NVP-CLR457 (compound 40) is an orally active, potent and balanced pan-class I PI3K inhibitor. NVP-CLR457 shows a clear dose-dependent PK/PD/efficacy relationship. NVP-CLR457 has antitumor activity[1].
IC50 & Target
PI3Kα
12 ± 1.5 nM (IC50)
PI3Kβ
8.3 ± 1.0 nM (IC50)
PI3Kδ
8.3 ± 2.0 nM (IC50)
PI3Kγ
230 ± 31 nM (IC50)
体外研究 (In Vitro)
NVP-CLR457 (compound 40) shows the mTOR activity, with an IC50 of 2474 ± 722 nM, and inhibits RPS6 phosphorylation with an IC50 of 1633 ± 54 nM[1]. NVP-CLR457 has no impact on the DDR response at concentrations of 1 and 5 μM[1]. NVP-CLR457 has no effect on the rate of microtubule polymerization[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis
Cell Line:
U87MG cells[1]
Concentration:
0, 1. 4, 16, 63, 250, 1000 nM
Incubation Time:
24 h
Result:
Inhibited the readouts of class I PI3K activity in a dose-dependent manner, with IC50 and IC90 values of 100 and 507 nM determined for the inhibition of S473P-Akt, and had no significant change in the readouts of mTOR activity.
体内研究 (In Vivo)
NVP-CLR457 (compound 40) (athymic nude mice bearing xenotransplanted Rat1-myr-p110α tumors, 3-20 mg/kg, PO, daily for 8 days) shows a dose-dependent inhibition of tumor growth[1]. NVP-CLR457 (Mice bearing xenograft HBRX2524 human primary breast tumor, 40 mg/kg, PO, daily for 15 days) inhibits the tumor growth throughout the study[1]. NVP-CLR457 (male Sprague-Dawley rats, 1.0 mg/kg, IV; 3.0 mg/kg, PO; once) shows high level of oral exposure and bioavailability[1]. Pharmacokinetic Parameters of NVP-CLR457 in male Sprague-Dawley rats[1].
compound
40
CL (mL/min/kg)
22 ± 6
Vss (L/kg)
4.4 ± 0.2
t1/2 (h)
3.3 ± 0.2
AUC iv (nM*h)
1770 ± 443
oral F (%)
97 ± 20
HDM FA (%)
37
NVP-CLR457 (3 mg/kg (IV) and 10 mg/kg (PO) for female OF1 mice, 0.1 mg/kg (IV), 0.3 mg/kg (PO) for male beagle dogs, once) shows low clearance, moderate volume of distribution, and rapid absorption leading to moderate to long half-lives and high oral bioavailability[1]. Pharmacokinetic Parameters of NVP-CLR457 in female OF1 mice and male beagle dogs[1].
species
mouse
dog
PPB (%)
76
71
CL (mL/min/kg)
10
3 ± 0
Vss (L/kg)
2
1.5 ± 0.2
t1/2 (h)
2
11 ± 3
AUC iv (nM*h)
3580
11213 ± 1169
AUC po (nM*h)
1738
11034 ± 1531
oral F (%)
49
98 ± 14
Cmax (nM)
422
1121 ± 128
Tmax (h)
0.5
1.3 ± 0.6
NVP-CLR457 (0.3-100 mg/kg, PO, once) leads to under-proportional increases in exposure (both AUC and Cmax) and much longer Tmax values[1]. Pharmacokinetic Parameters of NVP-CLR457 in male Sprague Dawley rats, male beagle dogs[1].
species
rat
dog
dose (mg/kg)
3
30
100
0.3
3
AUC (nM*h)
1709 ± 362
913 ± 251
784 ± 342
12,970 ± 1828
11,213 ± 1169
Cmax (nM)
213 ± 61
41 ± 6
22 ± 4
1121 ± 128
309 ± 40
Tmax (h)
0.5-2
4–24
24
1-2
2-24
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Sprague Dawley rats (male)[1]
Dosage:
1 mg/kg (IV), 3 mg/kg (PO)
Administration:
IV or PO, once (Pharmacokinetic Analysis)
Result:
Showed high level of oral exposure and bioavailability.
Animal Model:
Female OF1 mice, male beagle dogs[1]
Dosage:
3 mg/kg (IV) and 10 mg/kg (PO) for mice, 0.1 mg/kg (IV), 0.3 mg/kg (PO) for dogs
Administration:
IV or PO, once (Pharmacokinetic Analysis)
Result:
Showed low clearance, moderate volume of distribution, and rapid absorption leading to moderate to long half-lives and high oral bioavailability.
Animal Model:
Male Sprague Dawley rats, male beagle dogs[1]
Dosage:
0.3, 3, 30, 100 mg/kg
Administration:
PO, once (Pharmacokinetic Analysis)
Result:
Led to under-proportional increases in exposure (both AUC and Cmax) and much longer Tmax values when it formulated as a suspension of the crystalline material.
Observed dose-dependent exposure and PD responses, and showed a dose-dependent inhibition of tumor growth. The 3 mg/kg dose achieved 80% S473P-Akt inhibition only at the 1 h time point; the 10 mg/kg dose at the 1 and 4 h time points; and the 20 mg/kg at the 1, 4, and 10 h time points, with a high level of inhibition remaining at the 14 h time point (76%).
Animal Model:
Mice bearing xenograft HBRX2524 human primary breast tumor[1] Dosage: 40 mg/kg
Dosage:
40 mg/kg
Administration:
PO, daily for 15 days
Result:
Inhibited the tumor growth throughout the study, and showed a significant level of regression the end of the 15 day treatment period.
分子量
455.39
Formula
C18H20F3N7O4
CAS 号
1453082-52-4
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Fairhurst RA, et al. Identification of NVP-CLR457 as an Orally Bioavailable Non-CNS-Penetrant pan-Class IA Phosphoinositol-3-Kinase Inhibitor. J Med Chem. 2022 May 2.
NVP-BAG956 is an ATP-competitive PI3K inhibitor with IC50s of 34, 56, 112 and 444 nM for PI3Kδ, PI3Kα, PI3Kγ and PI3Kβ, respectively.
IC50 & Target[1]
PI3Kα
56 nM (IC50)
PI3Kβ
446 nM (IC50)
PI3Kδ
35 nM (IC50)
PI3Kγ
117 nM (IC50)
VEGFR1
2.56 μM (IC50)
PDK1
240 nM (IC50)
体外研究 (In Vitro)
NVP-BAG956 also inhibits PDK1 with an IC50 of 240/260 nM. NVP-BAG956 also inhibits VEGFR1 with an IC50 of 2.56±0.56 μM. NVP-BAG956 blocks phosphorylation of PKB/Akt in A2058 cells with an IC50 value of 67±25 nM. Inhibition of PKB/Akt phosphorylation correlated with loss of A2058 cell proliferation for NVP-BAG956 (IC50=290±20 nM). In the presence of NVP-BAG956, A2058 cells are only able to exit G2-M and then remain in G1. The p27 Kip1 expression is clearly induced by NVP-BAG956 in A2058 cells but not in C32 cells[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
427.50
Formula
C28H21N5
CAS 号
853910-02-8
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Marone R, et al. Targeting melanoma with dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors. Mol Cancer Res. 2009 Apr;7(4):601-13.
Cell Assay [1]
One day after plating (7×103 cells/cm2), melanoma cells (A2058, B16F1, B16F10, C32, HBL, Malme, Malme3M, NA8, SKMel2, SKMel23, A375, Hs294T, WM35, and 1205lu cells) are exposed to LY294002 (25 μM), Wortmannin (500 nM), NVP-BAG956 (1 μM), NVP-BBD130 (1 μM), NVP-BEZ235 (1 μM), and ZSTK474 (1 μM), and Rapamycin (100 nM). Compound concentrations are set 2 log units above the IC50 in vitro to ensure full PI3K inhibition, except for the μM inhibitor LY294002. Cells are trypsinized and counted, and the volume is quantified using a Casy Counter and Analyser. To determine the nuclear volume, cells are resuspended in CASYton containing 0.5% Triton X-100, followed by repetitive pipetting (8×), before volume measurements[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Marone R, et al. Targeting melanoma with dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors. Mol Cancer Res. 2009 Apr;7(4):601-13.
BGT226 (NVP-BGT226) is a PI3K (with IC50s of 4 nM, 63 nM and 38 nM for PI3Kα, PI3Kβ and PI3Kγ)/mTOR dual inhibitor which displays potent growth-inhibitory activity against human head and neck cancer cells[1][2].
IC50 & Target[1]
PI3Kα
4 nM (IC50)
PI3Kβ
63 nM (IC50)
PI3Kγ
38 nM (IC50)
mTOR
Autophagy
体外研究 (In Vitro)
BGT226 shows significant growth inhibition or signal blockage profiles compared with LY294002 and Rapamycin. BGT226 (10-10000 nM) inhibits FaDu and OECM1 cells growth with IC50s of 23.1±7.4 and 12.5±5.1 nM, respectively[2]. The expression levels of p-mTOR Ser2481 are decreased in BGT226-treated cell lines (200 nM; 24 hours) and both p-AKT Ser473 and p-mTOR Ser2448 are also decreased in BGT226-treated cell lines[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay[2]
Cell Line:
FaDu cells; OECM1 cells
Concentration:
10, 100, 1000, 10000 nM
Incubation Time:
Result:
Inhibited FaDu and OECM1 cells growth with IC50s of 23.1±7.4 and 12.5±5.1 nM, respectively.
Western Blot Analysis[2]
Cell Line:
FaDu cells; OECM1 cells
Concentration:
200 nM
Incubation Time:
24 hours
Result:
p-mTOR Ser2481 expression levels decreased, and both p-AKT Ser473 and p-mTOR Ser2448 expression levels also decreased.
体内研究 (In Vivo)
BGT226 (2.5 and 5 mg/kg; oral administration for 21 days in male athymic mice) causes 34.7% and 76.1% reduction of the tumor growth on day 21 compared with control[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Male athymic mice (strain BALB/cAnN.Cg-Foxn1nu/CrlNarl) with FaDu cell xenografted mouse model[2]
Dosage:
2.5 and 5 mg/kg
Administration:
Oral administration; 21 days
Result:
Caused 34.7% and 76.1% reduction of the tumor growth.
Clinical Trial
分子量
534.53
Formula
C28H25F3N6O2
CAS 号
915020-55-2
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Markman B, et al. Phase I safety, pharmacokinetic, and pharmacodynamic study of the oral phosphatidylinositol-3-kinase and mTOR inhibitor BGT226 in patients with advanced solid tumors. Ann Oncol. 2012 Sep;23(9):2399-408.
[2]. Chang KY, et al. Novel phosphoinositide 3-kinase/mTOR dual inhibitor, NVP-BGT226, displays potent growth-inhibitory activity against human head and neck cancer cells in vitro and in vivo. Clin Cancer Res. 2011 Nov 15;17(22):7116-26.
NVP-ACC789 is an inhibitor of human VEGFR-1, VEGFR-2 (mouse VEGFR-2), VEGFR-3 and PDGFR-β with IC50s of 0.38, 0.02 (0.23), 0.18, 1.4 μM, respectively.
IC50 & Target
VEGFR-2
0.02 μM (IC50)
VEGFR-1
0.38 μM (IC50)
mVEGFR-2
0.23 μM (IC50)
VEGFR-3
0.18 μM (IC50)
PDGFR-β
1.4 μM (IC50)
体外研究 (In Vitro)
The enzymatic kinase assays demonstrate that NVP-ACC789 is an inhibitor of human VEGFR-1, VEGFR-2 (mouse VEGFR-2), VEGFR-3 and PDGFR-β with IC50s of 0.38, 0.02 (0.23), 0.18, 1.4 μM, respectively. In VEGF-treated cultures, addition of the VEGFR-2 inhibitor NVP-ACC789 reduces BME cell number to baseline levels from 1 μM. Likewise, bFGF-induced BME cell proliferation is reduced markedly by NVP-ACC789 from 1 to 10 μM, without however reaching basal levels. NVP-ACC789 is found to be a potent inhibitor of VEGF-induced HUVE cell proliferation with an IC50 of 1.6 nM. NVP-ACC789 also completely inhibits VEGF-induced BME and BAE cell invasion and VEGF-C-induced BAE cell invasion. The inhibition is dose-dependent in both cell types with a maximal effect from 1 μM[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
NVP-ACC789 which is given in daily oral doses for 6 days blocks VEGF-induced angiogenesis in a dose-dependent manner. NVP-ACC789 also inhibits the response to bFGF to some extent, but the dose-response curve is not linear for NVP-ACC789[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
405.29
Formula
C21H17BrN4
CAS 号
300842-64-2
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Tille JC, et al. Vascular endothelial growth factor (VEGF) receptor-2 antagonists inhibit VEGF- and basicfibroblast growth factor-induced angiogenesis in vivo and in vitro. J Pharmacol Exp Ther. 2001 Dec;299(3):1073-85.
Kinase Assay [1]
Human VEGFR-2-transfected CHO cells are seeded into 6-well plates and grown to about 80% confluency. NVP-ACC789 is added in serial dilutions and the cells incubated for 2 h at 37°C in medium without fetal calf serum (FCS). VEGF (20 ng/mL) is then added. After a 5-min incubation at 37°C, the cells are washed twice with ice-cold phosphate-buffered saline and lysed. Nuclei are removed by centrifugation for 10 min at 4°C. Protein concentrations of the lysates are determined[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay [1]
HUVE cell proliferation is determined. Cells are seeded into 1.5% gelatin-coated 96-well plates (5×103 cells per well) and incubated in endothelial cell growth medium containing 5% fetal calf serum (FCS) for 24 h. The medium is replaced with essential basic medium (1.5% FCS), and the cells are incubated for another 24 h. Essential basic medium is then replaced with fresh medium containing either 50 ng/mL VEGF or 0.5 ng/mL bFGF. NVP-ACC789 is added just before addition of growth factors. The cells are incubated for a further 24 h before adding the BrdU labeling solution. Twenty four hours later, the labeling solution is removed, the cells are fixed, and the incorporated BrdU is visualized with a peroxidase-labeled anti-BrdU antibody and TMB substrate[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1]
Porous Teflon chambers (volume, 0.5 mL) filled with 0.8% w/v agar-containing heparin (20 U/mL) with or without VEGF (2 μg/mL) or bFGF (0.3 μg/mL) are implanted subcutaneously on the dorsal flank of female mice. The mice are treated with NVP-ACC789 (p.o. once daily) or vehicle (5% dimethyl sulfoxide, 1% Tween 80 in water) starting 1 day before implantation of the chamber and continuing for 5 days thereafter. At the end of the treatment period, the mice are killed, and the chambers are removed. The vascularized tissue growing around the chamber is removed carefully and weighed, and the blood content is assessed by measuring hemoglobin levels. The percentage inhibition of the angiogenic response (increase in tissue weight or total blood) is calculated. EC50 values are estimated from the dose response curves (% inhibition versus dose). Each experiment is performed with six animals per dose group and each dose is tested in at least two independent experiments[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Tille JC, et al. Vascular endothelial growth factor (VEGF) receptor-2 antagonists inhibit VEGF- and basicfibroblast growth factor-induced angiogenesis in vivo and in vitro. J Pharmacol Exp Ther. 2001 Dec;299(3):1073-85.
Panobinostat (LBH589; NVP-LBH589) is a potent and orally active non-selective HDAC inhibitor, and has antineoplastic activities[1][2]. Panobinostat induces HIV-1 virus production even at low concentration range 8-31 nM, stimulates HIV-1 expression in latently infected cells[4]. Panobinostat induces cell apoptosis and autophagy. Panobinostat can be used for the study of refractory or relapsed multiple myeloma[3].
IC50 & Target[1][5]
HDAC
HIV-1
体外研究 (In Vitro)
Panobinosta (LBH589) induces apoptosis of both MOLT-4 and Reh cells in a time- and dose-dependent manner. Panobinosta treatment results in histone (H3K9 and H4K8) hyperacetylation and regulation of cell-cycle control genes in Reh cells[1]. Panobinostat exhibites potent antiproliferative activity in human NSCLC cell lines with the IC50 ranging from 5 to 100 nM[2].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
Panobinosta (10, 20 mg/kg, i.p.) significantly slows tumor growth derived from Meso and NSCLC cells in vivo models. Panobinosta markedly increases acetylation of histone H3 and H4 of H69 human SCLC cells harvest from SCID mice[2]. Panobinostat (5, 10 and 20 mg/kg i.p.) demonstrates a clear benefit of decreased tumor burden, significantly improves TTE and reduces bone density loss in a disseminated multiple myeloma mouse model[3].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
349.43
Formula
C21H23N3O2
CAS 号
404950-80-7
中文名称
帕比司他
运输条件
Room temperature in continental US; may vary elsewhere.
Solubility: 2.5 mg/mL (7.15 mM); Suspended solution; Need ultrasonic
*以上所有助溶剂都可在 MCE 网站选购。
参考文献
[1]. Scuto A, et al. The novel histone deacetylase inhibitor, LBH589, induces expression of DNA damage response genes and apoptosis in Ph- acute lymphoblastic leukemia cells. Blood. 2008 May 15;111(10):5093-100.
[2]. Crisanti MC, et al. The HDAC inhibitor panobinostat (LBH589) inhibits mesothelioma and lung cancer cells in vitro and in vivo with particular efficacy for small cell lung cancer. Mol Cancer Ther. 2009 Aug;8(8):2221-31.
[3]. Ocio EM, et al. In vitro and in vivo rationale for the triple combination of panobinostat (LBH589) and dexamethasone with either bortezomib or lenalidomide in multiple myeloma. Haematologica. 2010 May;95(5):794-803.
[4]. Banerjee NS, et al. Vorinostat, a pan-HDAC inhibitor, abrogates productive HPV-18 DNA amplification. Proc Natl Acad Sci U S A. 2018 Nov 20;115(47):E11138-E11147.
[5]. Barton K, et al. Broad activation of latent HIV-1 in vivo. Nat Commun. 2016;7:12731. Published 2016 Sep 8.
Cell Assay [1]
Cells are washed with ice-cold PBS containing 0.1 mM sodium orthovanadate, and total proteins are isolated using RIPA lysis buffer, which includes protease inhibitors (leupeptin, antipain, and aprotinin), 0.5 mM PMSF, and 0.2 mM sodium orthovanadate. Protein amounts are quantified using the Bio-Rad protein assay. Equal amounts of proteins are loaded onto an sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gel, transferred onto nitrocellulose membrane, and probed with the antibody of interest: mouse monoclonal c-Myc and mouse monoclonal p21 antibodies; rabbit polyclonal phospho-Histone H2A.X, rabbit polyclonal acetyl-Histone H3 (Lys9), and rabbit polyclonal acetyl-Histone H4 (Lys8) antibodies; mouse monoclonal p27/KIP1 antibody; mouse monoclonal anti-β-actin; and mouse monoclonal anti-GADD45G. Membranes are then washed, reprobed with appropriate horseradish peroxidase-conjugated secondary antibodies, and developed with SuperSignal chemiluminescent substrate.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1]
AE17 and TC-1 cancer cells (1×106 cells) are injected into the flanks of adult female C57Bl/6 mice and severe combined immunodeficiency (SCID) mice. M30 (10×106 cells), A549 (5×106 cells), H69 (2.5×106 cells), BK-T (6.5×106), H526 (10×106), and RG1 (10×106) cells are also injected, but in the presence of matrigel, into the flanks of SCID mice. When tumors reach 100 to 500 mm3, panobinostat is administered via i.p. injections (10-20 mg/kg) on a daily schedule (5-days-on, 2-days-off regimen) for the entire duration of the experiment. Control micereceive i.p. injections with dextrose 5% in water. Every tumor is measured with a caliper at least twice weekly. For evaluation of the effects of combination therapy on SCLC-derived tumors, SCID mice with H69 tumors are administered panobinostat. Three days after the initiation of panobinostat, and again 1 wk later, etoposide (40 mg/kg) is administered i.p.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Scuto A, et al. The novel histone deacetylase inhibitor, LBH589, induces expression of DNA damage response genes and apoptosis in Ph- acute lymphoblastic leukemia cells. Blood. 2008 May 15;111(10):5093-100.
[2]. Crisanti MC, et al. The HDAC inhibitor panobinostat (LBH589) inhibits mesothelioma and lung cancer cells in vitro and in vivo with particular efficacy for small cell lung cancer. Mol Cancer Ther. 2009 Aug;8(8):2221-31.
[3]. Ocio EM, et al. In vitro and in vivo rationale for the triple combination of panobinostat (LBH589) and dexamethasone with either bortezomib or lenalidomide in multiple myeloma. Haematologica. 2010 May;95(5):794-803.
[4]. Banerjee NS, et al. Vorinostat, a pan-HDAC inhibitor, abrogates productive HPV-18 DNA amplification. Proc Natl Acad Sci U S A. 2018 Nov 20;115(47):E11138-E11147.
[5]. Barton K, et al. Broad activation of latent HIV-1 in vivo. Nat Commun. 2016;7:12731. Published 2016 Sep 8.
NVP-TAE 226 (TAE226) is a potent and ATP-competitive dual FAK and IGF-1R inhibitor with IC50s of 5.5 nM and 140 nM, respectively. NVP-TAE 226 (TAE226) also effectively inhibits Pyk2 and insulin receptor (InsR) with IC50s of 3.5 nM and 44 nM, respectively[1][2].
NVP-TAE 226 (TAE226), a potent ATP-competitive inhibitor of several tyrosine protein kinases, in particular FAK and IGF-IR kinases. In a cell-based kinase assays, FAK, IGF-IR kinase, and IR kinase are inhibited with an IC50 range of 100 to 300 nM compared with the other kinases tested, which are >10-fold less sensitive. In culture, NVP-TAE 226 inhibits extracellular matrix-induced autophosphorylation of FAK (Tyr395). NVP-TAE 226 also inhibits IGF-I-induced phosphorylation of IGF-IR and activity of its downstream target genes such as MAPK and Akt. NVP-TAE 226 retards tumor cell growth as assessed by a cell viability assay and attenuates G2-M cell cycle progression associated with a decrease in cyclin B1 and phosphorylated cdc2 (Tyr15) protein expression. NVP-TAE 226 treatment inhibits tumor cell invasion by at least 50% compared with the control in an in vitro Matrigel invasion assay. Interestingly, TAE226 treatment of tumor cells containing wild-type p53 mainly exhibits G2-M arrest, whereas tumor cells bearing mutant p53 underwent apoptosis[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
Treatment with NVP-TAE 226 (TAE226) at 50 or 75 mg/kg extends the median survival of U87 xenograft animals by 6 and 7 days, respectively (P=0.084 and P=0.042, respectively, compared with vehicle-treated animals). However, NVP-TAE 226 treatment of LN229-engrafted animals significantly prolongs their median survival by 19 days (P<0.004 for both dosages, compared with vehicle-treated animals)[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
468.94
Formula
C23H25ClN6O3
CAS 号
761437-28-9
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Liu TJ, et al. Inhibition of both focal adhesion kinase and insulin-like growth factor-I receptor kinase suppresses glioma proliferation in vitro and in vivo. Mol Cancer Ther, 2007, 6(4), 1357-1367.
[2]. Delimont D, et al. Laminin α2-mediated focal adhesion kinase activation triggers Alport glomerular pathogenesis. PLoS One. 2014 Jun 10;9(6):e99083.
[3]. Lietha D, et al. Crystal structures of the FAK kinase in complex with TAE226 and related bis-anilino pyrimidine inhibitors reveal a helical DFG conformation. PLoS One. 2008;3(11):e3800.
Cell Assay [1]
Glioma cell cultures are harvested with 0.05% trypsin and seeded in triplicate at 2×104 in 24-well culture plates for 24 h before drug treatment. Culture medium is used for mock treatment. Cells are harvested at the indicated day after treatment, and viable cells are counted using the Vi-cell viability analyzer. The antiproliferative activity of NVP-TAE 226 (ranging from 0.25 to 1 μM) on cells growing in culture is determined using a tetrazolium-based colorimetric MTT assay[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1]
Mice[1] Male nude mice used for this study are 6 to 8 weeks old. In DMEM/F12 serum-free media (5 μL), 5×105 of U87 cells and 1×106 of LN229 cells per mouse are implanted intracranially through a guide-screw system. Four days after injection of the tumor cells, mice are randomized into three groups for each cell line (n=6). Mice in group 1 are treated with 50 mg/kg NVP-TAE 226 in 200 μL of 0.5% methylcellulose, via an oral gavage. The mice in group 2 receive 75 mg/kg NVP-TAE 226 in 200 μL of 0.5% methylcellulose. The mice in group 3 the same vehicle used for administration of NVP-TAE 226 (control). Treatment frequency is once a day for 5 days and off for 2 days, for a duration of 4 weeks. Mice are monitored daily. Mice are euthanized when they are moribund, and the whole brain is extracted for rapid freezing in liquid nitrogen and storage at -70°C.
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Liu TJ, et al. Inhibition of both focal adhesion kinase and insulin-like growth factor-I receptor kinase suppresses glioma proliferation in vitro and in vivo. Mol Cancer Ther, 2007, 6(4), 1357-1367.
[2]. Delimont D, et al. Laminin α2-mediated focal adhesion kinase activation triggers Alport glomerular pathogenesis. PLoS One. 2014 Jun 10;9(6):e99083.
[3]. Lietha D, et al. Crystal structures of the FAK kinase in complex with TAE226 and related bis-anilino pyrimidine inhibitors reveal a helical DFG conformation. PLoS One. 2008;3(11):e3800.
NVP 231 is a potent, specific, and reversible ceramide kinase (CerK) inhibitor(IC50=12 nM) that competitively inhibits binding of ceramide to CerK[1]. NVP 231 induces cell apoptosis by increasing DNA fragmentation and caspase-3 and caspase-9 cleavage[2].
IC50 & Target
IC50: 12 nM (CerK); apoptosis[1][3]
体外研究 (In Vitro)
NVP-231 (0-500 nM; 24 hours) gradually reduces the cellular CerK activity, as measured by NBD-C1P formation, demonstrating that NVP-231 active in transfected cells. The IC50 for CerK in this cellular system is 59.70 ± 12 nM[3]. NVP-231 (0-1000 nM; 48 hours) decreases cell viability as a dose-dependent manner. This compound shows IC50 values of 1 μM in MCF-7 cells and 500 nM in NCI-H358 cells[3]. NVP-231 (1 μM; 24-72 hours) induces caspase-3 and caspase-9 cleavage in both cell lines. However, the highest caspase-3 and caspase-9 cleavage and activation occurred at 24 hours in MCF-7 cells, then decreases again. In NCI-H358 cells, caspase-3 and caspase-9 cleavage occurrs continuously over 72 hours[3]. NVP-231 (0-500 nM; 24 hours) causes a concentration-dependent up-regulation of cyclin B1 phosphorylation at Ser133 and a reduction of CDK1 phosphorylation at Tyr15. The total CDK1 expression also declined upon CerK inhibition[3].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay[3]
Cell Line:
MCF-7 cells; NCI-H358 cells
Concentration:
0 nM, 10 nM, 100 nM, 300 nM, 500 nM, 1000 nM
Incubation Time:
48 hours
Result:
Reduced MCF-7 cells and NCI-H358 cells in a concentration manner.
Apoptosis Analysis[3]
Cell Line:
MCF-7 cells; NCI-H358 cells
Concentration:
1000 nM
Incubation Time:
24-72 hours
Result:
Increases caspase-3 and caspase-9 cleavage in MCF-7 and NCI-H358 cells.
Western Blot Analysis[3]
Cell Line:
MCF-7 cells; NCI-H358 cells
Concentration:
0 nM, 100 nM, 300 nM, 500 nM
Incubation Time:
24 hours
Result:
Decreased p-cyclin B1, p-CDK1 as a concentration manner.
分子量
431.55
Formula
C25H25N3O2S
CAS 号
362003-83-6
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Graf C, et al. Targeting ceramide metabolism with a potent and specific ceramide kinase inhibitor. Mol Pharmacol. 2008 Oct;74(4):925-32.
[2]. Graf C, et al. A secondary assay for ceramide kinase inhibitors based on cell growth inhibition by short-chain ceramides. Anal Biochem. 2009 Jan 1;384(1):166-9.
[3]. Pastukhov O,et al. The ceramide kinase inhibitor NVP-231 inhibits breast and lung cancer cell proliferation by inducing M phase arrest and subsequent cell death.Br J Pharmacol. 2014 Dec;171(24):5829-44.
NVP-CGM097 is a potent and selective MDM2 inhibitor with IC50 of 1.7±0.1 nM for hMDM2.
IC50 & Target
IC50: 1.7±0.1 nM (hMDM2)[1]
体外研究 (In Vitro)
NVP-CGM097 binds to human MDM2 with an IC50 of 1.7 nM and shows high selectivity over MDM4 (IC50=2000 nM). NVP-CGM097 is about four times more potent than Nutlin-3a (IC50=8 nM). In addition, NVP-CGM097 shows no significant activity against Bcl-2:Bak, Bcl-2:Bad, Mcl-1:Bak, Mcl-1:NOXA, XIAP:BIR3, and c-IAP:BIR3 protein-protein interactions. NVP-CGM097 significantly inhibits the proliferation of cells expressing wild-type p53, while sparing the p53 null cells with a 35-58-fold difference. NVP-CGM097 is able to significantly redistribute wild-type p53 into the cell nucleus with an IC50 of 0.224 μM, demonstrating its ability to inhibit the p53:MDM2 interaction in living cells. In addition, NVP-CGM097 activity against the p53:MDM2 interaction is assessed in proliferation assays using either wild-type p53 or p53 null cells. NVP-CGM097 significantly inhibits the proliferation of cells expressing wild-type p53, while sparing the p53 null cells with a 35-58-fold difference. NVP-CGM097 inhibtis HCT116 (p53WT/WT) with IC50 of 454±136 nM[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
NVP-CGM097 is able to inhibit the interaction between p53 and MDM2 and reactivate the p53 pathway in vivo in a MDM2-amplified SJSA-1 human tumor model, as judged by elevation of p21 mRNA levels, a pharmacodynamic (PD) indicator for p53 activity. p21 mRNA levels are found to increase concomitantly with levels of NVP-CGM097 in tumor-bearing rats dosed at 30 mg/kg. The PD response is biphasic and prolonged up to 24 h. Additional p53 target genes such as MDM2 and PUMA mRNA levels are assessed in the tumor samples as well and showed a similar behavior. Daily treatment with NVP-CGM097 dose dependently and significantly inhibits SJSA-1 tumor growth in rats. It promotes stable disease at 20 mg/kg, which is associated with a plasma AUC0-24 of 163 μM•h. After iv administration, the total blood clearance (CL) of NVP-CGM097 is 5 mL/min per kg for mouse, 7 mL/min per kg for rat, 3 mL/min per kg for dog, and 4 mL/min per kg for monkey. The apparent terminal half-life (t1/2) is long in rodents and monkey (6-12 h) but is comparatively longer in dogs (20 h). After oral dosing, NVP-CGM097 is well absorbed with Tmax occurring between 1 and 4.5 h in all species tested[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
659.26
Formula
C38H47ClN4O4
CAS 号
1313363-54-0
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Holzer P, et al. Discovery of a Dihydroisoquinolinone Derivative (NVP-CGM097): A Highly Potent and Selective MDM2 Inhibitor Undergoing Phase 1 Clinical Trials in p53wt Tumors. J Med Chem. 2015 Aug 27;58(16):6348-58
Cell Assay [1]
Two pairs of cell lines are used to assess NVP-CGM097 p53-dependent antiproliferative effects: (1) an isogenic pair of HCT116 cell lines either expressing wild-type p53 or knocked-out for the p53 gene and (2) a nonisogenic pair of osteosarcoma cell lines either endogenously expressing wild-type p53 and amplified for MDM2 (SJSA-1 cells) or null for p53 (SAOS-2 cells)[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1]
Rats[1] Female athymic rats bearing subcutaneous xenotransplants of SJSA-1 tumors (n=5-12) are treated at 5, 10, 20, or 30 mg/kg or three times a week on Monday, Wednesday, and Friday (3qw M, W, F) at 30 or 70 mg/kg po for 14 days. Plasma AUCs are determined at the end of the study. Positive numbers indicate the percentage of tumor growth inhibition (T/C); negative numbers indicate the percentage of tumor regression.
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Holzer P, et al. Discovery of a Dihydroisoquinolinone Derivative (NVP-CGM097): A Highly Potent and Selective MDM2 Inhibitor Undergoing Phase 1 Clinical Trials in p53wt Tumors. J Med Chem. 2015 Aug 27;58(16):6348-58
NVP-TNKS656 is a highly potent, selective, and orally active TNKS2 inhibitor with IC50 of 6 nM, and is > 300 fold selectivity against PARP1 and PARP2.
IC50 & Target[1]
TNKS2
6 nM (IC50)
PARP2
32 μM (IC50)
体内研究 (In Vivo)
NVP-TNKS656 (30 or 100 mg/kg, p.o.) exhibits good exposure and moderate oral bioavailability of 32% and 53%, respectively. Some slight overproportional increase in oral exposure is observed between 30 and 100 mg/kg with the dose normalized AUC for the 100 mg/kg dose being 2-fold higher than for the 30 mg/kg dose. Mice treated with NVP-TNKS656 (350 mg/kg, p.o.) show good plasma and tumor exposures corresponding to AUC0-24h of 515 and 325 μM·h, respectively[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
494.58
Formula
C27H34N4O5
CAS 号
1419949-20-4
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Shultz MD, et al. Identification of NVP-TNKS656: the use of structure-efficiency relationships to generate a highly potent, selective, and orally active tankyrase inhibitor. J Med Chem. 2013 Aug 22;56(16):6495-511.
Animal Administration [1]
Athymic female nude mice weighing 19-22 g are implanted subcutaneously with a 3×3×3 mm3 tumor fragment from an MMTV-Wnt1 tumor-bearing mouse. Tumors are grown to approximately 250-300 mm3. Individual mice are given a single oral dose of vehicle (n=3) (4% HCl:10% propylene glycol:20% Solutol HS15:60.5% D5W:0.5% NaOH) or TNKS656 at 350 mg/kg (n=18). At 0.5, 1, 2, 4, 8, 16, or 24 h following dosing (n=3/time point), mice are euthanized, and blood is collected via cardiac puncture and processed for plasma. Tumors are excised from mice and frozen at −80°C for PD analysis.
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Shultz MD, et al. Identification of NVP-TNKS656: the use of structure-efficiency relationships to generate a highly potent, selective, and orally active tankyrase inhibitor. J Med Chem. 2013 Aug 22;56(16):6495-511.
NVP-ADW742 (ADW742) is an orally active, selective IGF-1R tyrosine kinase inhibitor with an IC50 of 0.17 μM. NVP-ADW742 inhibits insulin receptor (InsR) with an IC50 of 2.8 μM. NVP-ADW742 induces pleiotropic antiproliferative/proapoptotic biologic sequelae in tumor cells[1][2].
IC50 & Target
IC50: 0.17 μM (IGF-1R) and 2.8 μM (InsR)[1]
体外研究 (In Vitro)
NVP-ADW742 (ADW742; 0.1-10 µM; 72 hours) dose-dependently inhibits serum-induced cell growth in all cell lines[1]. NVP-ADW742 (0.1-9 µM; 20 min) blocks IGF-1-induced phosphorylation of IGF-1R and its known downstream target Akt at submicromolar concentrations[1]. NVP-ADW742 has much higher IC50 values for other kinases (IC50>10 μM for HER2, PDGFR, VEGFR-2, or Bcr-Abl p210; and IC50>5 μM for c-Kit)[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay[1]
Cell Line:
A panel of cell lines from multiple myeloma (MM), other hematologic malignancies and solid tumors
Concentration:
0.1, 0.5, 1, 2, 5, 10 µM
Incubation Time:
72 hours
Result:
Dose-dependently inhibited serum-induced cell growth in all cell lines.
Western Blot Analysis[1]
Cell Line:
NWT-21 cells
Concentration:
0.1, 0.3, 1, 3, 9 µM
Incubation Time:
20 min
Result:
Blocked IGF-1-induced phosphorylation of IGF-1R and its known downstream target Akt at submicromolar concentrations.
体内研究 (In Vivo)
NVP-ADW742 (ADW742; 10 mg/kg for IP or 50 mg/kg for orally; twice daily for 19 days) significantly suppresses tumor growth and prolongs the survival of mice[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
6- to 8-week-old male SCID/NOD mice with diffuse skeletal lesions of luciferase-expressing MM cells[1]
Dosage:
10 mg/kg (IP) or 50 mg/kg (orally)
Administration:
IP or orally; twice daily for 19 days
Result:
Significantly suppressed tumor growth and prolonged the survival of mice.
分子量
453.58
Formula
C28H31N5O
CAS 号
475488-23-4
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Mitsiades CS, et al. Inhibition of the insulin-like growth factor receptor-1 tyrosine kinase activity as a therapeutic strategy for multiple myeloma, other hematologic malignancies, and solid tumors. Cancer Cell. 2004 Mar;5(3):221-30.
[2]. Warshamana-Greene GS, et al. The insulin-like growth factor-I (IGF-I) receptor kinase inhibitor NVP-ADW742, in combination with STI571, delineates a spectrum of dependence of small cell lung cancer on IGF-I and stem cell factor signaling. Mol Cancer Ther. 2004 May;3(5):527-35.
NVP-2 is a potent and selective ATP-competitive cyclin dependent kinase 9 (CDK9) probe, inhibits CDK9/CycT activity with an IC50 of 0.514 nM. NVP-2 displays inhibitory effcts on CDK1/CycB, CDK2/CycA and CDK16/CycY kinases with IC50 values of 0.584 µM, 0.706 µM, and 0.605 µM, respectively. NVP-2 induces cell apoptosis.[1]
IC50 & Target
CDK9
0.5 nM (IC50)
体外研究 (In Vitro)
NVP-2 has an anti-proliferation of leukemia cells, inhibits KOPT-K1, Jurkat, P12-ICHIKAWA, DU.528, MOLT 16, HSB-2, PF-382, SKW-3, SUP-T11, DND-41 and HPB-ALL cells with IC50 values of 0.1688 µM, 0.1233 µM,0.5736 µM,0.1575 µM, 0.1620 µM,0.1585 µM, 0.1808 µM, 0.2589 µM, 0.0918 µM and 0.3023 µM, respectively[1]. NVP-2 (250 nM-1 μM; 6 hours) engages CDK9 in wildtype and CRBN−/− MOLT4 cells at all concentrations, while CDK2 and CDK7 are unaffected[1]. NVP-2 (0-10 nM; 72 hours) exhibits CRBN-dependent anti-proliferative and pro-apoptotic effects in MOLT4 cells, displays an IC50 value of 9 nM[1]. NVP-2 (250 nM; 24 hours) induces cell apoptosis in MOLT4 cells, upregulates caspase-3 and γH2A.X expression. However, while the compound washout significantly reduces the degree of apoptosis induced by NVP-2[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay[1]
Cell Line:
Leukemia cell lines
Concentration:
0.1233 µM-0.5736 µM
Incubation Time:
72 hours
Result:
Inhibited Leukemia cell lines viabity.
Western Blot Analysis[1]
Cell Line:
Wildtype and CRBN−/− MOLT4 cells
Concentration:
1 μM; 500 nM; 250 nM
Incubation Time:
6 hours
Result:
Degrade CDK9 sub-stoichiometrically at all concentrations.
Apoptosis Analysis[1]
Cell Line:
Wildtype and CRBN−/− MOLT4 cells
Concentration:
250 nM
Incubation Time:
24 hours
Result:
Induced cell apoptosis in cells and wash outed the compound relieved NVP-2-induced cell apoptosis.
Cell Proliferation Assay[1]
Cell Line:
MOLT4 cells
Concentration:
0-10 nM
Incubation Time:
72 hours
Result:
Exhibited anti-proliferative effects in MOLT4 cells.
分子量
513.07
Formula
C27H37ClN6O2
CAS 号
1263373-43-8
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Winter GE, et al. BET Bromodomain Proteins Function as Master Transcription Elongation Factors Independent of CDK9 Recruitment.Mol Cell. 2017 Jul 6;67(1):5-18.e19.
Nav1.7-IN-2 是一种有效的 PI3K 抑制剂，IC50 为 10 nM，详细信息可参考专利文献US7998990B2 中的化合物 Example 8。
NVP-QAV-572 Chemical Structure
CAS No. : 957209-68-6
规格
价格
是否有货
数量
10 mM * 1 mL in DMSO
￥3110
In-stock
5 mg
￥3000
In-stock
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￥4500
In-stock
50 mg
￥12000
In-stock
100 mg
￥18000
In-stock
200 mg
询价
500 mg
询价
* Please select Quantity before adding items.
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生物活性
NVP-QAV-572 is a PI3K inhibitor extracted from patent US7998990B2, Compound Example 8, has an IC50 of 10 nM.
IC50 & Target[1]
PI3K
10 nM (IC50)
体外研究 (In Vitro)
NVP-QAV-572 (Example 8) is useful in the treatment of conditions which are mediated by the activation of the Pi3 kinase enzymes, particularly inflammatory or allergic conditions[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
471.50
Formula
C17H19F2N7O3S2
CAS 号
957209-68-6
运输条件
Room temperature in continental US; may vary elsewhere.
Siremadlin (NVP-HDM201) is a potent, orally bioavailable and highly specific p53-MDM2 interaction inhibitor.
体外研究 (In Vitro)
Siremadlin (NVP-HDM201) disrupts both human and murine TP53- MDM2 interactions, with nanomolar cellular IC50 values, blocking TP53 degradation[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
Siremadlin (NVP-HDM201) is an imidazolopyrrolidinone analogue, showing a very advantageous in vivo profile. NVP-HDM201 has recently entered Phase 1 clinical trials in cancer patients[2]. Constitutive PB mutagenesis in Arf−/− mice provides a collection of spontaneous tumors with characterized insertional genetic landscapes. Tumors are allografted in large cohorts of mice to assess the pharmacologic effects of Siremadlin (NVP-HDM201). Sixteen out of 21 allograft models are sensitive to Siremadlin (NVP-HDM201) but ultimately relapse under treatment. A comparison of tumors with acquired resistance to Siremadlin (NVP-HDM201) and untreated tumors identified 87 genes that are differentially and significantly targeted by the PB transposon[1]. Siremadlin (NVP-HDM201) administered either daily at a low dose or once at a high dose revealed a differentiated engagement of the p53 molecular response. In contrast to the daily low dose treatment regimen, the single high dose Siremadlin (NVP-HDM201) regimen results in a rapid and dramatic induction of p53-dependent PUMA expression and apoptosis. This is consistent with the finding that a single high dose Siremadlin (NVP-HDM201) treatment, administered orally or intravenously, results in a robust and sustained tumor regression. Overall, both daily and once every 3 weeks dosing regimen shows comparable long term efficacy in preclinical studies. The ongoing clinical trial is currently designed to compare both dosing regimens with regard to efficacy and tolerability[3].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
555.41
Formula
C26H24Cl2N6O4
CAS 号
1448867-41-1
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Chapeau EA, et al. Resistance mechanisms to TP53-MDM2 inhibition identified by in vivo piggyBac transposon mutagenesis screen in an Arf-/- mouse model. Proc Natl Acad Sci U S A. 2017 Mar 21;114(12):3151-3156.
[2]. Furet P, et al. Discovery of a novel class of highly potent inhibitors of the p53-MDM2 interaction by structure-based design starting from a conformational argument. Bioorg Med Chem Lett. 2016 Oct 1;26(19):4837-41.
[3]. Stéphane F, et al. Abstract 1224: Insights into the mechanism of action of NVP-HDM201, a differentiated and versatile Next-Generation small-molecule inhibitor of Mdm2, under evaluation in phase I clinical trials. Insights into the mechanism of action of NVP-HDM201, a differentiated and versatile Next-Generation small-molecule inhibitor of Mdm2, under evaluation in phase I clinical trials. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1224.
NVP-BSK805 is an ATP-competitive JAK2 inhibitor, with IC50s of 0.48 nM, 31.63 nM, 18.68 nM, and 10.76 nM for JAK2 JH1 (JAK homology 1), JAK1 JH1, JAK3 JH1, and TYK2 JH1, respectively[1].
IC50 & Target[1]
JAK2 JH1
0.48 nM (IC50)
FL JAK2 V617F
0.56 nM (IC50)
FL JAK2 wt
0.58 nM (IC50)
TYK2 JH1
10.76 nM (IC50)
JAK3 JH1
18.68 nM (IC50)
JAK1 JH1
31.63 nM (IC50)
体外研究 (In Vitro)
NVP-BSK805 (BSK 805) is a JAK2 inhibitor, with IC50s of 0.48 nM, 31.63 nM, 18.68 nM, and 10.76 nM for JAK2 JH1 (JAK homology 1), JAK1 JH1, JAK3 JH1, and TYK2 JH1, respectively. NVP-BSK805 inhibits the full-length wild-type JAK2 (FL JAK2 wt) and FL JAK2 V617F activity, with IC50s of 0.58 ± 0.03 and 0.56 ± 0.04 nM. NVP-BSK805 is ATP-competitive, with aclculated Ki of 0.43 ± 0.02 nM. NVP-BSK805 suppresses the growth of JAK2V617F-bearing acute myeloid leukemia cell lines with GI50 of <100 nm. nvp-bsk805 blocks the stat5 phosphorylation at ≥100 nm concentrations, and shows a bias for jak2 over jak1 jak3 inhibition in jak2V617F-mutant cell lines[1]. NVP-BSK805 (5 μM) improves P-gp inhibitory activity. NVP-BSK805 increases sensitization of drug-resistant KBV20C cancer cells to VIC treatment at 10 μM, and such an effect is more effective than a 5 μM dose[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
NVP-BSK805 (BSK 805; 150 mg/kg, p.o.) blocks STAT5 phosphorylation, splenomegaly, and leukemic cell spreading in a Ba/F3 JAK2V617F cell-driven mouse model[1]. NVP-BSK805 (50, 75, and 100 mg/kg, p.o.) also suppresses rhEpo-mediated polycythemia and splenomegaly in BALB/c mice[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
490.55
Formula
C27H28F2N6O
CAS 号
1092499-93-8
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Baffert F, et al. Potent and selective inhibition of polycythemia by the quinoxaline JAK2 inhibitor NVP-BSK805. Mol Cancer Ther. 2010 Jul;9(7):1945-55.
[2]. Cheon JH, et al. The JAK2 inhibitors CEP-33779 and NVP-BSK805 have high P-gp inhibitory activity and sensitize drug-resistant cancer cells to vincristine. Biochem Biophys Res Commun. 2017 Sep 2;490(4):1176-1182.
Cell Assay [1]
The antiproliferative activity of JAK2 inhibitors is determined by incubating cells for 72 hours (96 hours for MB-02 and MUTZ-8 cells) with an 8-point concentration range of NVP-BSK805 and cell proliferation relative to NVP-BSK805 is measured using the colorimetric WST-1 cell viability readout. Of each triplicate treatment, the mean is calculated and these data are plotted in XLfit 4 to determine the half-maximal growth inhibition (GI50) values[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1]
Mice[1] Concomitantly with NVP-BSK805 treatment, female BALB/c mice receive daily s.c. injections (in 100 μL saline buffer) of 10 units of rhEpo for 4 consecutive days. Controls are injected corresponding volumes of saline buffer. Mice are sacrificed 24 hours after the final dose and total blood, spleen, and bone marrow are taken for further analysis. Animals are 8 to 10 weeks of age at treatment start (20-25 g body weight) and are kept under optimal hygienic conditions with free access to food and water[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Baffert F, et al. Potent and selective inhibition of polycythemia by the quinoxaline JAK2 inhibitor NVP-BSK805. Mol Cancer Ther. 2010 Jul;9(7):1945-55.
[2]. Cheon JH, et al. The JAK2 inhibitors CEP-33779 and NVP-BSK805 have high P-gp inhibitory activity and sensitize drug-resistant cancer cells to vincristine. Biochem Biophys Res Commun. 2017 Sep 2;490(4):1176-1182.
VER-82576 (NVP-BEP800) is a potent, orally available and selective Hsp90 inhibitor, with an IC50 of 58 nM for Hsp90β; VER-82576 also slightly blocks Grp94 and Trap-1, with IC50s of 4.1 and 5.5 μM, respectively.
IC50 & Target[1]
HSP90β
58 nM (IC50)
GRP94
4.1 μM (IC50)
TRAP-1
5.5 μM (IC50)
体外研究 (In Vitro)
VER-82576 (NVP-BEP800) is a potent and selective Hsp90 inhibitor, with an IC50 of 58 nM for Hsp90β and is >70-fold selective against Grp94 and Trap-1, with IC50s of 4.1 ± 1.1 and 5.5 ± 0.48 μM. VER-82576 potently inhibits the proliferation of tumor cells, with GI50s ranging from 38 nM in A375 cells to 1050 nM in PC3 cells, with an average GI50 of 245 nM. VER-82576 (250-1250 nM) depletes client proteins in human cancer cell lines in vitro[1]. VER-82576 (NVP-BEP800; 200 nM) shows no significant effect on the ionizing radiation (IR) dose-response curves of A549 cells, and is less toxic to SNB19 cells. VER-82576 in combination with IR results in more severe DNA damage in both A549 and SNB19 cell lines than each treatment alone and also protracts the kinetics of DNA damage repair in SNB19 cells[2]. VER-82576 (NVP-BEP800; 0.05, 0.1 or 0.2 μM) dose-dependently decreases the viability and induces apoptosis of glioblastoma cells. VER-82576 (0.2 μM) suppresses the expression of IKKβ protein but does not alter the levels of IKKβ mRNA in T98G cells. VER-82576 (0.2 μM) suppresses the expression of heat shock protein 70[3].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
VER-82576 (NVP-BEP800; 15 or 30 mg/kg, p.o.) shows antitumor activities in A375 cancer xenografts and BT-474 xenograft-bearing mice[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
480.41
Formula
C21H23Cl2N5O2S
CAS 号
847559-80-2
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Massey AJ, et al. Preclinical antitumor activity of the orally available heat shock protein 90 inhibitor NVP-BEP800. Mol Cancer Ther. 2010 Apr;9(4):906-19.
[2]. Niewidok N, et al. Hsp90 Inhibitors NVP-AUY922 and NVP-BEP800 May Exert a Significant Radiosensitization on Tumor Cells along with a Cell Type-Specific Cytotoxicity. Transl Oncol. 2012 Oct;5(5):356-69. Epub 2012 Oct 1.
[3]. Wu J, et al. Irradiation facilitates the inhibitory effect of the heat shock protein 90 inhibitor NVP-BEP800 on the proliferation of malignant glioblastoma cells through attenuation of the upregulation of heat shock protein 70. Exp Ther Med. 2014 Sep;8(3):893-898. Epub 2014 Jun 23.
Cell Assay [3]
Prior to treatments, the cells are placed into 6-well plates in medium at a density of 1 × 105 cells/well, three wells per treatment group and cultured for 24 h. The cells are divided into treatment groups and treated accordingly for 40 h: vehicle control (DMSO, 0.016%, v/v), VER-82576 (0.05, 0.1 or 0.2 μM), irradiation (10 Gy), or VER-82576 (0.05, 0.1 or 0.2 μM) in combination with irradiation (10 Gy). Upon completion of the treatment, all cells are incubated with 0.5 mg/ml MTT for 3 h. The relative viability of the treated cells to the untreated control cells is measured. The absorbance is measured at 490 nm on a microplate reader[3].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1]
The estrogen receptor (ER)-positive, ErbB2-overexpressing cell line BT-474 is grown in DMEM high glucose (4.5 g/L) supplemented with 10% FCS, 200 mM l-glutamine, and 1% sodium pyruvate (BioConcept). Two or 3 d before cell inoculation, each mouse is s.c. implanted on the upper dorsal side with a 17β-estradiol pellet (25 μg/d; 90-d release) using a trocar needle. BT-474 cells (5 × 106) are injected in 200 μL Matrigel/HBSS (1:1 volume) s.c. in the right flank. The A375 cell line expresses mutant B-Raf (V600E). The cells are grown in RPMI 1640 supplemented with 10% FCS and 200 mM l-glutamine. To establish tumors, 5 × 106 A375 cells are injected s.c. in 200 μL PBS in the right flank. The animals are kept under optimized hygienic conditions with a 12-h dark, 12-h light cycle. The animals are fed food and water ad libitum. Tumor growth and body weights are monitored at regular intervals. The xenograft tumor sizes are measured manually with calipers, and the tumor volume is estimated using the following formula: (W × L × H × π/6), where width (W), length (L), and height (H) are the three largest diameters. Treatment with VER-82576 is initiated when the average tumor volume reaches 100 to 300 mm3[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Massey AJ, et al. Preclinical antitumor activity of the orally available heat shock protein 90 inhibitor NVP-BEP800. Mol Cancer Ther. 2010 Apr;9(4):906-19.
[2]. Niewidok N, et al. Hsp90 Inhibitors NVP-AUY922 and NVP-BEP800 May Exert a Significant Radiosensitization on Tumor Cells along with a Cell Type-Specific Cytotoxicity. Transl Oncol. 2012 Oct;5(5):356-69. Epub 2012 Oct 1.
[3]. Wu J, et al. Irradiation facilitates the inhibitory effect of the heat shock protein 90 inhibitor NVP-BEP800 on the proliferation of malignant glioblastoma cells through attenuation of the upregulation of heat shock protein 70. Exp Ther Med. 2014 Sep;8(3):893-898. Epub 2014 Jun 23.
NVP-TAE 684 (TAE 684) is a highly potent and selective ALK inhibitor, which blocks the growth of ALCL-derived and ALK-dependent cell lines with IC50 values between 2 and 10 nM[1].
IC50 & Target
IC50: 2-10 nM (ALK-dependent cell lines)[1]
体外研究 (In Vitro)
TAE684 inhibits the proliferation of Ba/F3 NPM-ALK cells with an IC50 of 3 nM, without affecting the survival of parental Ba/F3 cells at concentrations up to 1 μM. TAE684 inhibits STAT3 and STAT5 phosphorylation in a dose-dependent manner in both Ba/F3 NPM-ALK and Karpas-299 cells. TAE684 induces apoptosis and G1 phase arrest in NPM-ALK-expressing Ba/F3 cells and ALCL patient cell lines[1]. NVP-TAE684 markedly reduces cell survival in both sensitive H3122 and H3122 CR cells, but has little to no effect on the viability of other, non-ALK-dependent cancer cell lines. NVP-TAE684 treatment of H3122 CR cells suppresses phosphorylation of ALK, AKT, and ERK and induces marked apoptosis. TAE684 potently suppresses the survival of Ba/F3 cells expressing the EML4-ALK L1196M mutant[2]. Neurite outgrowth induced by expression of the mALKR1279Q mutant is completely inhibited at 30 nM NVP-TAE684, which is comparable with the response seen with activated wt mALK[3].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
NVP-TAE684 suppresses lymphomagenesis in two independent models of ALK-positive ALCL and induces regression of established Karpas-299 lymphomas. TAE684 displays appreciable bioavailability and half-life in vivo. TAE684 (1, 3, and 10 mg/kg. p.o.) significantly delays in lymphoma development and shows 100- to 1,000-fold reduction in luminescence signal. The TAE684- (10 mg/kg) treated group appeares healthy and does not display any signs of compound- or disease-related toxicity[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
614.20
Formula
C30H40ClN7O3S
CAS 号
761439-42-3
运输条件
Room temperature in continental US; may vary elsewhere.
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献
[1]. Galkin AV, et al. Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK. Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):270-5.
[2]. Katayama R, et al. Therapeutic strategies to overcome PF-02341066 resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK. Proc Natl Acad Sci U S A. 2011 May 3;108(18):7535-40.
[3]. Schonherr C, Activating ALK mutations found in neuroblastoma are inhibited by PF-02341066 and NVP-TAE684. Biochem J. 2011 Dec 15;440(3):405-13.
Cell Assay [1]
Luciferase-expressing Karpas-299, SU-DHL-1, and Ba/F3 cells and transformed Ba/F3 stably expressing NPM-ALK, BCR-ABL, or TEL-kinase fusion constructs are plated in 384-well plates (25,000 cells per well) and incubated with serial dilutions of TAE684 or DMSO for 2-3 days. Luciferase expression is used as a measure of cell proliferation/survival and is evaluated with the Bright-Glo Luciferase Assay System. ICsub>50 values are generated by using XLFit software.
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1]
For in vivo compound efficacy studies, treatment is initiated 72 h after tail vein injection of 1×106 Karpas-299-, Ba/F3 NPM-ALK- or BCR-ABL-expressing cells into female Fox Chase SCIDBeige mice. Mice (n=10 per group) are administered either TAE684 resuspended in 10% 1-methyl-2-pyrrolidinone/90% PEG 300 solution at 1, 3, and 10 mg/kg once daily for 3 weeks or the vehicle solution at the same dosing schedule. Disease progression and compound efficacy is monitored weekly with bioluminescence imaging. To determine the efficacy of TAE684 on established disease, dosing is initiated on day 12, at which time the disease confirmed to be widespread by bioluminescence imaging. For analysis of downstream molecular effects in vivo, mice with established lymphomas are administered vehicle solution or TAE684 (10 mg/kg) for 3 days. At the end of treatment, mice are killed, and lymph nodes are extracted for immunoblotting and histological analysis.
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Galkin AV, et al. Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK. Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):270-5.
[2]. Katayama R, et al. Therapeutic strategies to overcome PF-02341066 resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK. Proc Natl Acad Sci U S A. 2011 May 3;108(18):7535-40.
[3]. Schonherr C, Activating ALK mutations found in neuroblastoma are inhibited by PF-02341066 and NVP-TAE684. Biochem J. 2011 Dec 15;440(3):405-13.
NVP-BSK805 trihydrochloride trihydrochloride is an ATP-competitive JAK2 inhibitor, with IC50s of 0.48 nM, 31.63 nM, 18.68 nM, and 10.76 nM for JAK2 JH1 (JAK homology 1), JAK1 JH1, JAK3 JH1, and TYK2 JH1, respectively[1].
IC50 & Target[1]
JAK2 JH1
0.48 nM (IC50)
JAK2(V617F)
0.56 nM (IC50)
FL JAK2 wt
0.58 nM (IC50)
TYK2 JH1
18.68 nM (IC50)
JAK1 JH1
31.68 nM (IC50)
体外研究 (In Vitro)
NVP-BSK805 trihydrochloride (BSK 805) is a JAK2 inhibitor, with IC50s of 0.48 nM, 31.63 nM, 18.68 nM, and 10.76 nM for JAK2 JH1 (JAK homology 1), JAK1 JH1, JAK3 JH1, and TYK2 JH1, respectively. NVP-BSK805 trihydrochloride inhibits the full-length wild-type JAK2 (FL JAK2 wt) and FL JAK2 V617F activity, with IC50s of 0.58 ± 0.03 and 0.56 ± 0.04 nM. NVP-BSK805 trihydrochloride is ATP-competitive, with aclculated Ki of 0.43 ± 0.02 nM. NVP-BSK805 trihydrochloride suppresses the growth of JAK2V617F-bearing acute myeloid leukemia cell lines with GI50 of <100 nm. nvp-bsk805 trihydrochloride blocks the stat5 phosphorylation at ≥100 nm concentrations, and shows a bias for jak2 over jak1 jak3 inhibition in jak2V617F-mutant cell lines[1]. NVP-BSK805 trihydrochloride (5 μM) improves P-gp inhibitory activity. NVP-BSK805 trihydrochloride increases sensitization of drug-resistant KBV20C cancer cells to VIC treatment at 10 μM, and such an effect is more effective than a 5 μM dose[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
NVP-BSK805 trihydrochloride (BSK 805; 150 mg/kg, p.o.) blocks STAT5 phosphorylation, splenomegaly, and leukemic cell spreading in a Ba/F3 JAK2V617F cell-driven mouse model[1]. NVP-BSK805 trihydrochloride (50, 75, and 100 mg/kg, p.o.) also suppresses rhEpo-mediated polycythemia and splenomegaly in BALB/c mice[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
599.93
Formula
C27H31Cl3F2N6O
CAS 号
2320258-95-3
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Baffert F, et al. Potent and selective inhibition of polycythemia by the quinoxaline JAK2 inhibitor NVP-BSK805. Mol Cancer Ther. 2010 Jul;9(7):1945-55.
[2]. [2].Cheon JH, et al. The JAK2 inhibitors CEP-33779 and NVP-BSK805 have high P-gp inhibitory activity and sensitize drug-resistant cancer cells to vincristine. Biochem Biophys Res Commun. 2017 Sep 2;490(4):1176-1182.
[1]. Tröster A, et al. NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. ChemMedChem. 2018 Aug 20;13(16):1629-1633.
NVP-BSK805 dihydrochloride is an ATP-competitive JAK2 inhibitor, with IC50s of 0.48 nM, 31.63 nM, 18.68 nM, and 10.76 nM for JAK2 JH1 (JAK homology 1), JAK1 JH1, JAK3 JH1, and TYK2 JH1, respectively[1].
IC50 & Target[1]
JAK2 JH1
0.48 nM (IC50)
FL JAK2 V617F
0.56 nM (IC50)
FL JAK2 wt
0.58 nM (IC50)
TYK2 JH1
10.76 nM (IC50)
JAK3 JH1
18.68 nM (IC50)
JAK1 JH1
31.63 nM (IC50)
体外研究 (In Vitro)
NVP-BSK805 dihydrochloride (BSK805 dihydrochloride) is a JAK2 inhibitor, with IC50s of 0.48 nM, 31.63 nM, 18.68 nM, and 10.76 nM for JAK2 JH1 (JAK homology 1), JAK1 JH1, JAK3 JH1, and TYK2 JH1, respectively. NVP-BSK805 inhibits the full-length wild-type JAK2 (FL JAK2 wt) and FL JAK2 V617F activity, with IC50s of 0.58 ± 0.03 and 0.56 ± 0.04 nM. NVP-BSK805 is ATP-competitive, with aclculated Ki of 0.43 ± 0.02 nM. NVP-BSK805 suppresses the growth of JAK2V617F-bearing acute myeloid leukemia cell lines with GI50 of <100 nm. nvp-bsk805 blocks the stat5 phosphorylation at ≥100 nm concentrations, and shows a bias for jak2 over jak1 jak3 inhibition in jak2V617F-mutant cell lines[1]. NVP-BSK805 dihydrochloride (5 μM) improves P-gp inhibitory activity. NVP-BSK805 increases sensitization of drug-resistant KBV20C cancer cells to VIC treatment at 10 μM, and such an effect is more effective than a 5 μM dose[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
NVP-BSK805 (BSK805 dihydrochloride; 150 mg/kg, p.o.) blocks STAT5 phosphorylation, splenomegaly, and leukemic cell spreading in a Ba/F3 JAK2V617F cell-driven mouse model[1]. NVP-BSK805 (50, 75, and 100 mg/kg, p.o.) also suppresses rhEpo-mediated polycythemia and splenomegaly in BALB/c mice[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
563.47
Formula
C27H30Cl2F2N6O
CAS 号
1942919-79-0
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Baffert F, et al. Potent and selective inhibition of polycythemia by the quinoxaline JAK2 inhibitor NVP-BSK805. Mol Cancer Ther. 2010 Jul;9(7):1945-55.
[2]. Cheon JH, et al. The JAK2 inhibitors CEP-33779 and NVP-BSK805 have high P-gp inhibitory activity and sensitize drug-resistant cancer cells to vincristine. Biochem Biophys Res Commun. 2017 Sep 2;490(4):1176-1182.
Cell Assay [1]
The antiproliferative activity of JAK2 inhibitors is determined by incubating cells for 72 hours (96 hours for MB-02 and MUTZ-8 cells) with an 8-point concentration range of NVP-BSK805 and cell proliferation relative to NVP-BSK805 is measured using the colorimetric WST-1 cell viability readout. Of each triplicate treatment, the mean is calculated and these data are plotted in XLfit 4 to determine the half-maximal growth inhibition (GI50) values[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1]
Mice[1] Concomitantly with NVP-BSK805 treatment, female BALB/c mice receive daily s.c. injections (in 100 μL saline buffer) of 10 units of rhEpo for 4 consecutive days. Controls are injected corresponding volumes of saline buffer. Mice are sacrificed 24 hours after the final dose and total blood, spleen, and bone marrow are taken for further analysis. Animals are 8 to 10 weeks of age at treatment start (20-25 g body weight) and are kept under optimal hygienic conditions with free access to food and water[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Baffert F, et al. Potent and selective inhibition of polycythemia by the quinoxaline JAK2 inhibitor NVP-BSK805. Mol Cancer Ther. 2010 Jul;9(7):1945-55.
[2]. Cheon JH, et al. The JAK2 inhibitors CEP-33779 and NVP-BSK805 have high P-gp inhibitory activity and sensitize drug-resistant cancer cells to vincristine. Biochem Biophys Res Commun. 2017 Sep 2;490(4):1176-1182.
Fevipiprant (QAW039; NVP-QAW039) is a selective, potent, reversible competitive CRTh2 antagonist with an in vitro dissociation constant KD value of 1.1nM at the CRTh2 receptor and an IC50 value of 0.44 nM for inhibition of PGD2-induced eosinophil shape change in human whole blood. IC50:0.44 nM(PGD2-induced eosinophil shape change) Kd value:1.1nM(CRTh2 receptor)[1] In vitro: CRTh2-mediated shape change in eosinophils was used to profile QAW039 in whole blood and represents a physiologically relevant environment. The comparable IC50 values for QAW039 in the whole blood and isolated shape-change assays are consistent with its lower plasma-protein binding and its relatively slow dissociation kinetics that drive its increased potency .QAW039 is highly potent in whole-blood systems, with the IC50 value obtained consistent with the affinity values calculated from radioligand experiments. In a further disease-relevant cellular context, the potency of QAW039 in the isolated Th2 cell cytokine inhibition assay is consistent with its CRTh2 receptor affinity, and, as with eosinophil assay readouts, this represents an improved potency compared with QAV680[2].
Clinical Trial
分子量
426.41
Formula
C19H17F3N2O4S
CAS 号
872365-14-5
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Erpenbeck, V. J. et al. Pharmacokinetics, Safety, and Tolerability of Fevipiprant (QAW039), a Novel CRTh2 Receptor Antagonist: Results From 2 Randomized, Phase 1, Placebo-Controlled Studies in Healthy Volunteers. Clinical pharmacology in drug development 5, 306-313, doi:10.1002/cpdd.244 (2016).
[2]. Sykes, D. A. et al.Fevipiprant (QAW039), a Slowly Dissociating CRTh2 Antagonist with the Potential for Improved Clinical Efficacy. Molecular pharmacology 89, 593-605, doi:10.1124/mol.115.101832 (2016).
