BRD7-IN-1 free base, a modified derivative of BI7273 (BRD7/9 inhibitor), binds to a VHL ligand via a linker to form a PROTAC VZ185 (VZ185 against BRD7/9 with DC50s of 4.5 and 1.8 nM, respectively)[1].
IC50 & Target
BRD7, BRD9[1]
分子量
394.47
Formula
C22H26N4O3
CAS 号
2305379-66-0
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]. Zoppi V, et al. Iterative Design and Optimization of Initially Inactive Proteolysis Targeting Chimeras (PROTACs) Identify VZ185 as a Potent, Fast, and Selective von Hippel-Lindau (VHL) Based Dual Degrader Probe of BRD9 and BRD7. J Med Chem. 2019 Jan 24;62(2):699-726.
R406 free base 是一种有效的，具有口服活性的，ATP竞争性的 Syk/FLT3 抑制剂，Ki 为 30 nM，有效抑制 Syk 激酶活性，IC50 为 41 nM。R406 free base 可减轻免疫复合物介导的炎症。R406 free base 还抑制 Lyn (IC50=63 nM) 和 Lck (IC50=37 nM).
R406 free base Chemical Structure
CAS No. : 841290-80-0
规格
价格
是否有货
数量
Free Sample (0.1-0.5 mg)
Apply now
10 mM * 1 mL in DMSO
￥1729
In-stock
2 mg
￥810
In-stock
5 mg
￥1250
In-stock
10 mg
￥1989
In-stock
50 mg
￥6412
In-stock
100 mg
￥10114
In-stock
200 mg
询价
500 mg
询价
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R406 free base 相关产品
•相关化合物库:
Bioactive Compound Library Plus
Apoptosis Compound Library
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Anti-Blood Cancer Compound Library
生物活性
R406 free base is an orally available and competitive Syk/FLT3 inhibitor for ATP binding with a Ki of 30 nM, potently inhibits Syk kinase activity in vitro with an IC50 of 41 nM, measured at an ATP concentration corresponding to its Km value. R406 free base reduces immune complex-mediated inflammation[1]. R406 free base also inhibits Lyn (IC50=63 nM) and Lck (IC50=37 nM)[2].
R406 inhibits adenosine A3 receptor (IC50=0.081 µM), adenosine transporter (IC50=1.84 µM), and monoamine transporter (IC50=2.74 µM)[1]. R406 inhibits Huh7 hepatocyte, A549 epithelial, and H1299 lung cancer lines with EC50s of 15.1, 2.9 and 6.3 µM, respectively[1]. R406 inhibits phosphorylation of Syk substrate LAT in mast cells and BLNK/SLP65 in B 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.
Western Blot Analysis[1]
Cell Line:
Cultured human mast cells (CHMC)
Concentration:
0.016, 0.08, 0.4, 2 µM
Incubation Time:
40 minutes
Result:
Inhibited all other kinases tested at 5 to 100 fold less potency than Syk as judged by phosphorylation of target proteins.
体内研究 (In Vivo)
R406 (5 and 10 mg/kg) shows efficacy in the amelioration of the Arthus reaction and in reducing clinical symptoms in the collagen antibody-induced arthritis (CAIA) and K/BxN models of rheumatoid arthritis (RA). Immune complex (IC)-mediated inflammation is reduced by inhibition of Fc receptor signaling with R406[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:
Female Balb/c mice (6-8 weeks) with CAIA[1]
Dosage:
5 and 10 mg/kg
Administration:
Administered orally, b.i.d, for 14 days, starting 4 hours after antibody challenge on day 0.
Result:
Reduced inflammation and swelling, and the arthritis progressed more slowly in treated animals than in vehicle controls.
Animal Model:
Female C57BL/6 mice with arthritis[1]
Dosage:
10 mg/kg
Administration:
Administered orally one hour before serum injection; b.i.d; for 13 days
Result:
Delayed the onset and reduced the severity of clinical arthritis. Paw thickening and clinical arthritis were reduced by approximately 50%.
分子量
470.45
Formula
C22H23FN6O5
CAS 号
841290-80-0
运输条件
Room temperature in continental US; may vary elsewhere.
AFP464 free base (NSC710464 free base), is an active HIF-1α inhibitor with an IC50 of 0.25 μM, also is a potent aryl hydrocarbon receptor (AhR) activator.
IC50 & Target
IC50：0.25 μM (HIF-1α)[1]
Clinical Trial
分子量
448.44
Formula
C22H23F3N4O3
CAS 号
468719-52-0
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]. Terzuoli E1, Aminoflavone, a ligand of the aryl hydrocarbon receptor, inhibits HIF-1alpha expression in an AhR-independent fashion. Cancer Res. 2010 Sep 1;70(17):6837-48.
Toremifene (Z-Toremifene) is a second-generation selective estrogen-receptor modulator (SERM) in development for the prevention of osteoporosis. Toremifene also potent inhibits infectious EBOV Zaire and Marburg (MARV) with IC50 of 0.07 µM and 2.6 µM, respectively[1][2].
体外研究 (In Vitro)
Toremifene is a second-generation selective estrogen-receptor modulator (SERM) in development for the prevention of osteoporosis and other adverse effects resulting from ADT with prostate cancer[1]. The growth of Ac-1 cells was inhibited by tamoxifen, toremifene and atamestane in vitro with IC50values of 1.8±1.3μM, 1±0.3μM and 60.4±17.2μM, respectively. The combination of toremifene plusatamestane was found to be better than toremifene or atamestane alone in vitro[3].
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)
The effect of this combination was then studied in vivo using Ac-1 xenografts grown in ovariectomized female SCID mice. The mice were injected with toremifene (1000μg/day), atamestane (1000μg/day), tamoxifen (100μg/day), or the combination of toremifene plus atamestane. In this study, our results indicate that the combination of toremifene plus atamestane was as effective as toremifene or tamoxifen alone but may not provide any additional benefit over toremifene alone or tamoxifen alone[3].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
405.96
Formula
C26H28ClNO
CAS 号
89778-26-7
中文名称
托瑞米芬；涛瑞米芬
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]. Matthew R Smith, Selective Estrogen Receptor Modulators to Prevent Treatment-Related Osteoporosis.Rev Urol. 2005; 7(Suppl 3): S30-S35.
[2]. Laura Cooper, et al. Screening and Reverse-Engineering of Estrogen Receptor Ligands as Potent Pan-Filovirus Inhibitors. J Med Chem. 2020 Sep 4.
[3]. Gauri J Sabnis, Luciana Macedo, Olga Goloubeva, Toremifene – Atamestane; Alone or In Combination: Predictions from the Preclinical Intratumoral Aromatase Model. J Steroid Biochem Mol Biol. 2008 January; 108(1-2): 1-7.
[4]. Taneja SS, Morton R, Barnette G, Prostate cancer diagnosis among men with isolated high-grade intraepithelial neoplasia enrolled onto a 3-year prospective phase III clinical trial of oral toremifene. J Clin Oncol. 2013 Feb 10;31(5):523-9.
CKI-7 free base 是一种有效且 ATP 竞争性的酪蛋白激酶 1 (CK1) 抑制剂，IC50 为 6 μM，Ki 为 8.5 μM。CKI-7 free base 选择性抑制 Cdc7 激酶，还抑制 SGK，S6K1 以及 MSK1。CKI-7 free base 对酪蛋白激酶 II 和其他蛋白激酶的作用弱得多。
CKI-7 free base Chemical Structure
CAS No. : 120615-25-0
规格
价格
是否有货
数量
10 mM * 1 mL in DMSO
￥1572
In-stock
5 mg
￥850
In-stock
10 mg
￥1500
In-stock
25 mg
￥3750
In-stock
50 mg
￥6250
In-stock
100 mg
￥11200
In-stock
200 mg
询价
500 mg
询价
* Please select Quantity before adding items.
CKI-7 free base 相关产品
•相关化合物库:
Bioactive Compound Library Plus
Cell Cycle/DNA Damage Compound Library
Immunology/Inflammation Compound Library
Kinase Inhibitor Library
MAPK Compound Library
Metabolism/Protease Compound Library
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Anti-Cancer Compound Library
Anti-Aging Compound Library
Reprogramming Compound Library
Oxygen Sensing Compound Library
Glutamine Metabolism Compound Library
Anti-Breast Cancer Compound Library
Anti-Blood Cancer Compound Library
Anti-Cancer Metabolism Compound Library
生物活性
CKI-7 free base is a potent and ATP-competitive casein kinase 1 (CK1) inhibitor with an IC50 of 6 μM and a Ki of 8.5 μM. CKI-7 free base is a selective Cdc7 kinase inhibitor. CKI-7 free base also inhibits SGK, ribosomal S6 kinase-1 (S6K1) and mitogen- and stress-activated protein kinase-1 (MSK1). CKI-7 free base has a much weaker effect on casein kinase II and other protein kinases[1][2][3][4].
IC50 & Target[1][2][3]
CK1
6 μM (IC50)
CK1
8.5 μM (Ki)
Cdc7
SGK
S6K1
MSK1
体外研究 (In Vitro)
CKI-7 (0.1-10 μM; 5 days; ES cells) treatment significantly increases the expression of the early neuroectodermal marker Sox1 and the number of cells positive for the neural markers nestin and βIII-tubulin, in a concentration-dependent manner[1]. CKI-7 (5 μM; 5 days; ES cells) treatment suppresses SFEB-induced β-catenin stabilization on day 5, indicating that CKI-7 inhibits Wnt signaling[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.
RT-PCR[1]
Cell Line:
Mouse ES cells
Concentration:
0.1-10 μM
Incubation Time:
5 days
Result:
Significantly increased the expression of the early neuroectodermal marker Sox1 and the number of cells positive for the neural markers nestin and βIII-tubulin, in a concentration-dependent manner.
Western Blot Analysis[1]
Cell Line:
Mouse ES cells
Concentration:
5 μM
Incubation Time:
5 days
Result:
Suppressed SFEB-induced β-catenin stabilization on day 5.
体内研究 (In Vivo)
In vivo dose-dependent anti-tumor activity of CKI-7 is demonstrated in a SCID-Beige mouse systemic tumor model utilzing a recently isolated Philadelphia chromosome positive acute lymphoblastic leukemia cell line. Standard cell cycle synchronization studies established that exposure to CKI-7 results in cell cycle dependent caspase 3 activation and apoptotic cell death[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.
分子量
285.75
Formula
C11H12ClN3O2S
CAS 号
120615-25-0
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Osakada F, et al. In vitro differentiation of retinal cells from human pluripotent stem cells by small-molecule induction. J Cell Sci. 2009 Sep 1;122(Pt 17):3169-79.
[2]. Mark G. Frattini, et al. Small Molecule Inhibition of Cdc7, a Key Cell Cycle Regulator and Novel Therapeutic Target, Successfully Inhibits Leukemia Cell Growth in Vitro and in Vivo. Blood (2008) 112 (11): 2668.
[3]. Chijiwa T, et al. A newly synthesized selective casein kinase I inhibitor, N-(2-aminoethyl)-5-chloroisoquinoline-8-sulfonamide, and affinity purification of casein kinase I from bovine testis. J Biol Chem. 1989 Mar 25;264(9):4924-7.
[4]. Rena G, et al. D4476, a cell-permeant inhibitor of CK1, suppresses the site-specific phosphorylation and nuclear exclusion of FOXO1a. EMBO Rep. 2004 Jan;5(1):60-5.
Taletrectinib (DS-6051b) free base is a potent, orally active, and next-generation selective ROS1/NTRK inhibitor. Taletrectinib free base potently inhibits recombinant ROS1, NTRK1, NTRK2, and NTRK3 with IC50s of 0.207, 0.622, 2.28, and 0.98 nM, respectively. Taletrectinib free base also inhibits ROS1 G2032R and other Crizotinib-resistant ROS1 mutants[1][2].
体外研究 (In Vitro)
The IC50 of Taletrectinib free base (1-1000 nM; 72 hours) against Ba/F3-TPM3-NTRK1, Ba/F3-ETV6-NTRK1, -NTRK2, -NTRK3, or KM12 cells is ~3-20 nM[1]. Taletrectinib free base (0.001-1000 nM; 2 hours) dose dependently inhibited autophosphorylation of ROS1 in U-118-MG cells in vitro[1]. Taletrectinib (DS-6051b) free base potently inhibits autophosphorylation of ROS1 in JFCR-165, JFCR-168, and MGH193-1B cells[1]. Taletrectinib free base partially suppresses phospho-NTRK1 at 10 nM, and completely suppresses by 100 nM. Taletrectinib free base potently inhibits recombinant ROS1, NTRK1, and NTRK3 in sub-nanomolar concentration in an ATP-competitive manner. Taletrectinib free base almost completely inhibits ACK, ALK, DDR1, and LTK at 0.2 μM among 160 kinases in the presence of 1 mM ATP, but did not inhibit other 152 kinases strongly[1]. Taletrectinib free base effectively inhibits Crizotinib-resistant ROS1 secondary mutations, including G2032R solvent front mutation[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay[1]
Cell Line:
TPM3-NTRK1-induced Ba/F3 cells, KM12 cells
Concentration:
1-1000 nM
Incubation Time:
72 hours
Result:
Inhibited TPM3-NTRK1-induced Ba/F3 cells and KM12 cells viability.
Western Blot Analysis[1]
Cell Line:
U-118 MG cells (harboring FIG-ROS1 fusion gene)
Concentration:
0.001-1000 nM
Incubation Time:
2 hours
Result:
Dose dependently inhibited autophosphorylation of ROS1 in U-118-MG cells.
体内研究 (In Vivo)
Taletrectinib (DS-6051b) free base (25-200 mg/kg; p.o.; once daily for 18 days) shows antitumor activity[1]. Taletrectinib free base (6.25-200 mg/kg; p.o.; once daily for 8 days) inhibits NTRK-rearranged cancer in Balb-c nu/nu mice bearing KM12 cells[1]. Taletrectinib free base (3-100 mg/kg; p.o.; once daily for 4 days) shows rapid tumor regression in the wild-type (WT) and the G2032R-mutant Ba/F3-bearing mice without severe body weight loss[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Balb-c nu/nu mice (bearing U-118 MG cells)[1]
Dosage:
25, 50, 100, and 200 mg/kg
Administration:
P.o.; once daily for 18 days
Result:
Effectively inhibited tumor growth at ≥25 mg/kg without significant body weight loss.
Clinical Trial
分子量
405.47
Formula
C23H24FN5O
CAS 号
1505514-27-1
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]. Katayama R, et al. The new-generation selective ROS1/NTRK inhibitor DS-6051b overcomes crizotinib resistant ROS1-G2032R mutation in preclinical models. Nat Commun. 2019;10(1):3604. Published 2019 Aug 9.
[2]. Fujiwara Y, et al. Safety and pharmacokinetics of DS-6051b in Japanese patients with non-small cell lung cancer harboring ROS1 fusions: a phase I study. Oncotarget. 2018;9(34):23729-23737. Published 2018 May 4.
JNJ-63576253 (TRC-253) free base 是一种有效和具有口服活性的雄激素受体 (androgen receptor) 的完全拮抗剂，在 LNCaP 细胞中对 F877L 突变型 AR 和野生型 AR 的 IC50 值分别为 37 和 54 nM。JNJ-63576253 free base 可用于去势抵抗性前列腺癌 (CRPC) 的研究。
JNJ-63576253 free base Chemical Structure
CAS No. : 2110426-27-0
规格
是否有货
100 mg
询价
250 mg
询价
500 mg
询价
* Please select Quantity before adding items.
JNJ-63576253 free base 的其他形式现货产品:
JNJ-63576253
生物活性
JNJ-63576253 (TRC-253) free base is a potent and orally active full antagonist of androgen receptor (AR), with IC50s of 37 and 54 nM for F877L mutant AR and wild-type AR in LNCaP cells. JNJ-63576253 free base can be used for the research of castration-resistant prostate cancer (CRPC)[1].
IC50 & Target
IC50: 37 nM (F877L mutant AR in LNCaP cells); 54 nM (wild-type AR in LNCaP cells)[1]
体外研究 (In Vitro)
JNJ-63576253 (0.0003-100 μM; 5 d) inhibits the growth of VCaP cells, with an IC50 of 265 nM[1]. JNJ-63576253 is stable in human liver microsomes, with an T1/2 of >180 min[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)
JNJ-63576253 (30 mg/kg; p.o. once daily for 72 days) significantly inhibits the growth of prostate LNCaP SRα F877L tumor in mice[1]. JNJ-63576253 (30 mg/kg; p.o. once daily for 10 days) inhibits the five androgen sensitive organs (ASOs) under stimulation by testosterone propionate (TP) in mice[1]. JNJ-63576253 (10 mg/kg; p.o.) exhibits moderate oral bioavailability (45%), Cmax (0.66 μM) and AUClast (4.9 μg•h/mL) in mice[1]. JNJ-63576253 (2 mg/kg; i.v.) exhibits reasonable half-life (5.99 h), CL (15.0 mL/min/kg) and Vdss (6.11 L/kg) in mice[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Castrated SHO mice with prostate LNCaP SRα F877L tumor[1]
Dosage:
30 mg/kg
Administration:
P.o. once daily for 72 days
Result:
Inhibited the tumor growth by 87%.
Animal Model:
CD-1 male mice[1]
Dosage:
2 mg/kg for i.v.; 10 mg/kg for p.o. (Pharmacokinetic Analysis)
Administration:
Intravenous administration and oral administration
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]. Zhang Z, et, al. Discovery of JNJ-63576253: A Clinical Stage Androgen Receptor Antagonist for F877L Mutant and Wild-Type Castration-Resistant Prostate Cancer (mCRPC). J Med Chem. 2021 Jan 28;64(2):909-924.
Hu7691 free base 是一种具有口服活性的，选择性 Akt 抑制剂，对 Akt1、Akt2 和 Akt3 的 IC50 分别为 4.0 nM、97.5 nM、28 nM。Hu7691 free base 抑制肿瘤生长并降低小鼠的皮肤毒性。
Hu7691 free base Chemical Structure
CAS No. : 2241232-43-7
规格
是否有货
100 mg
询价
250 mg
询价
500 mg
询价
* Please select Quantity before adding items.
生物活性
Hu7691 free base is an orally active, selective Akt inhibitor with IC50s of 4.0 nM, 97.5 nM, 28 nM for Akt1, Akt2 and Akt3, respectively. Hu7691 free base inhibits tumor growth and enables decrease of cutaneous toxicity in mice[1].
IC50 & Target[1]
Akt1
4.0 nM (IC50)
Akt2
97.5 nM (IC50)
Akt3
28 nM (IC50)
PKA
11 nM (IC50)
PKCη
629 nM (IC50)
ROCK1
354 nM (IC50)
RSK1
756 nM (IC50)
p70S6K
229 nM (IC50)
体外研究 (In Vitro)
Hu7691 free base displays low inhibitions against most of the kinases in the four families (AGC, TK, TKL, Lipid/Atypical; PKA, IC50=11 nM; PKCη, IC50=629 nM; ROCK1, IC50=354 nM; RSK1, IC50=756 nM; P70S6K, IC50=229 nM; SGK, IC50=1009 nM)[1]. Hu7691 free base (2.25-36 μM; 24 hours) induces effective decrease of the phosphorylation level of Akt (S473)[1]. Hu7691 free base (10, 20, 30, 40 μM; for 72 h) exhibits low toxicity against HaCaT cells with an IC50 value of 15.2 μM[1]. Hu7691 free base has a significant inhibitory effect on the growth of 18 kinds of human tumor cells (U87-MG, U251, A549, HepG2, HT-29, KHOS, MDA-MB-231, PC3, SKOV3 and so on) derived from different tissues, with the IC50 range of 0.6-27 μM. Hu7691 free base shows low antiproliferation activities against the HL7702 and HPDE6-C7 normal cells, exhibiting IC50 values of 5.4 and 16.1 μM, respectively[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis[1]
Cell Line:
HaCaT cells
Concentration:
2.25, 4.5, 9, 18, 36 μM
Incubation Time:
24 hours
Result:
Induced effective decrease of the phosphorylation level of Akt (S473).
体内研究 (In Vivo)
Hu7691 free base (12.5-50 mg/kg/day; i.g.; for 22 days) shows dose-dependent tumor growth inhibition[1]. Hu7691 free base (15 mg/kg; oral) has a T1/2 of 8.68 hours, a Cmax of 171.17 ng/mL and an AUC of 2820.64 ng/mL•h in rats[1]. Hu7691 free base (2 mg/kg; iv) has a T1/2 of 6.24 hours, a Cmax of 207.52 ng/mL and an AUC of 532.87 ng/mL•h in rats[1]. Hu7691 free base (20 mg/kg; oral) has a T1/2 of 16.7 hours, a Cmax of 905.65 ng/mL and an AUC of 36303 ng/mL•h in beagle dog (male, 40 weeks old, 8–10 kg)[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Balb/c mice (nu/nu, female, 3-4 weeks old, 20-25 g) with 786-O and KHOS xenograft[1]
Dosage:
12.5, 25, 50 mg/kg
Administration:
Oral; once daily for 22 days
Result:
Showed dose-dependent tumor growth inhibition.
Animal Model:
SD rats (male, 8 weeks old, 250-300 g)[1]
Dosage:
15 mg/kg (Pharmacokinetic Analysis)
Administration:
Oral
Result:
Had a T1/2 of 8.68 hours, a Cmax of 171.17 ng/mL and an AUC of 2820.64 ng/mL•h.
分子量
414.42
Formula
C22H21F3N4O
CAS 号
2241232-43-7
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]. Jinxin Che, et al. Discovery of N-((3 S,4 S)-4-(3,4-Difluorophenyl)piperidin-3-yl)-2-fluoro-4-(1-methyl-1 H-pyrazol-5-yl)benzamide (Hu7691), a Potent and Selective Akt Inhibitor That Enables Decrease of Cutaneous Toxicity. J Med Chem. 2021 Aug 26;64(16):12163-12180.
Tamsulosin ((R)-(-)-YM12617 free base) is an inhibitor of α1-adrenergic receptor. Tamsulosin is used for the research of prostatic hyperplasia. Tamsulosin attenuates abdominal aortic aneurysm growth in animal models[1].
IC50 & Target[1]
α1-adrenergic receptor
Clinical Trial
分子量
408.51
Formula
C20H28N2O5S
CAS 号
106133-20-4
中文名称
坦索罗辛；坦洛新；坦索洛新
运输条件
Room temperature in continental US; may vary elsewhere.
MA242 free base 是特异性的 MDM2 和 NFAT1 双重抑制剂。MA242 free base 以高亲和力直接结合 MDM2 和 NFAT1，诱导 MDM2 和 NFAT1 蛋白降解，并抑制 NFAT1 介导的 MDM2 转录。MA242 free base 在胰腺癌细胞系中诱导凋亡。
MA242 free base Chemical Structure
CAS No. : 1049704-17-7
规格
是否有货
100 mg
询价
250 mg
询价
500 mg
询价
* Please select Quantity before adding items.
生物活性
MA242 free base is a specific dual inhibitor of MDM2 and NFAT1. MA242 free base directly binds both MDM2 and NFAT1 with high affinity, induces their protein degradation, and inhibits NFAT1-mediated transcription of MDM2. MA242 free base induces apoptosis in pancreatic cancer cell lines regardless of p53 status[1].
IC50 & Target
MDM2, NFAT1[1]
体外研究 (In Vitro)
MA242 (0.05-5 μM; 72 hours) free base significantly inhibits pancreatic cancer cell growth, with IC50s ranging from 0.1 to 0.4 μM, regardless of the p53 status of the cells. However, MA242 free base shows minimal effects on the growth of normal HPDE cells (IC50=5.81 μM), indicating that MA242 has selective effects against cancer cells[1]. MA242 (0.1-0.5 μM; 24 hours) free base significantly decreases the MDM2 and NFAT1 protein levels at a low concentration in all three cell lines[1]. MA242 free base decreases cell proliferation and induces apoptosis in pancreatic cancer cell lines regardless of p53 status[1]. MA242 free base alone or in combination with Gemcitabine inhibits pancreatic tumor growth and metastasis without any host toxicity[1]. MA242 free base exerts cytotoxicity against hepatocellular carcinoma (HCC) cells by inhibiting the NFAT1-MDM2 pathway in vitro, independent of p53. MA242 showed selective cytotoxicity against HCC cells, with IC50 values ranging from 0.1-0.31 μM[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay[1]
Cell Line:
The human pancreatic cancer HPAC, Panc-1, AsPC-1, Mia-Paca-2 and BxPC-3 cell lines; The human pancreatic ductal epithelium (HPDE) cell line
Concentration:
0.05, 0.5, and 5 μM
Incubation Time:
72 hours
Result:
The IC50s are 0.14, 0.14, 0.15, 0.25, 0.40, and 5.81 μM for Panc-1, Mia-Paca-2, AsPC-1, BxPC-3, HPAC, and HPDE cells, respectively.
Western Blot Analysis[1]
Cell Line:
The human pancreatic cancer HPAC, Panc-1, and AsPC-1 cell lines
Concentration:
0, 0.1, 0.2, and 0.5 μM
Incubation Time:
24 hours
Result:
Decreased the expression of MDM2 and NFAT1.
体内研究 (In Vivo)
MA242 (IP; 2.5, 5, 10 mg/kg) free base suppresses orthotopic pancreatic tumor growth in vivo, independent of p53[1]. There were no significant differences in the average body weights between the vehicle- and MA242 free base-treated mice in either of the models, did not have significant host toxicity at these effective doses[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
2.5 or 5 mg/kg for Panc-1 tumor-bearing mice; 10 mg/kg for AsPC-1 tumor-bearing mice
Administration:
IP; 2.5 or 5 mg/kg/d, 5 d/wk for five weeks for Panc-1 tumor-bearing mice; IP; 10 mg/kg/d, 5 d/wk for three weeks for AsPC-1 tumor-bearing mice
Result:
Resulted in 56.1% and 82.5% inhibition of tumor growth in nude mice bearing Panc-1 orthotopic tumors, respectively. Significantly suppressed the growth of AsPC-1 orthotopic tumors by 89.5% (P < 0.01) compared with the tumors in control animals. Led to almost complete tumor regression in MD242-treated mice in both models.
分子量
465.95
Formula
C24H20ClN3O3S
CAS 号
1049704-17-7
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]. Wei Wang, et al. Discovery and Characterization of Dual Inhibitors of MDM2 and NFAT1 for Pancreatic Cancer Therapy. Cancer Res. 2018 Oct 1;78(19):5656-5667.
[2]. Wei Wang, et al. MDM2-NFAT1 dual inhibitor, MA242: Effective against hepatocellular carcinoma, independent of p53. Cancer Lett. 2019 Sep 10;459:156-167.
Vatalanib (PTK787; ZK-222584; CGP-79787) is an inhibitor of VEGFR2/KDR with IC50 of 37 nM.
IC50 & Target
VEGFR2
37 nM (IC50)
体外研究 (In Vitro)
Vatalanib also inhibits Flk, c-Kit and PDGFRβ with IC50 of 270 nM, 730 nM and 580 nM, respectively. Vatalanib shows the anti-proliferation effect by inhibiting thymidine incorporation induced by VEGF in HUVECs with and IC50 of 7.1 nM, and dose-dependently suppresses VEGF-induced survival and migration of endothelial cells in the same dose range without cytotoxic or antiproliferative effect on cells that do not express VEGF receptors[1]. A recent study shows that Vatalanib significantly inhibits the growth of hepatocellular carcinoma cells and enhances the IFN/5-FU induced apoptosis by increasing proteins levels of Bax and reduced Bcl-xL and Bcl-2[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)
Vatalanib induces dose-dependent inhibition of the angiogenic response to VEGF and PDGF in both a growth factor implant model and a tumor cell-driven angiogenesis model after once-daily oral dosing (25-100 mg/kg). In the same dose range, Vatalanib also inhibits the growth and metastasesof several human carcinomas in nude mice without significant effect on circulating blood cells or bone marrow leukocytes[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
346.81
Formula
C20H15ClN4
CAS 号
212141-54-3
中文名称
瓦他拉尼碱
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.
溶解性数据
In Vitro:
DMSO : 125 mg/mL (360.43 mM; Need ultrasonic and warming)
配制储备液
浓度溶剂体积质量
1 mg
5 mg
10 mg
1 mM
2.8834 mL
14.4171 mL
28.8342 mL
5 mM
0.5767 mL
2.8834 mL
5.7668 mL
10 mM
0.2883 mL
1.4417 mL
2.8834 mL
参考文献
[1]. Wood JM, et al. PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. Cancer Res. 2000, 60(8
[2]. Murakami M, et al. Tyrosine kinase inhibitor PTK/ZK enhances the antitumor effects of interferon-α/5-fluorouracil therapy for hepatocellular carcinoma cells. Ann Surg Oncol. 2011, 18(2), 589-596.
[3]. Wan J, et al. Local recurrence of small cell lung cancer following radiofrequency ablation is induced by HIF-1α expression in the transition zone. Oncol Rep. 2016 Mar;35(3):1297-308.
Kinase Assay [1]
Each GST-fused kinase is incubated under optimized buffer conditions. ATP in a total volume of 30 μL in the presence or absence of a test substance (Vatalanib) for 10 min at ambient temperature. The reaction is stopped by adding 10 μL of 250 mM EDTA[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay [1]
Subconfluent HUVECs are seeded into 96-well plates coated with 1.5% gelatin. After 24 h, growth medium is replaced by basal medium containing 1.5% FCS and a constant concentration of VEGF (50 ng/mL), bFGF (0.5 ng/mL), or FCS (5%), in the presence or absence of Vatalanib. As a control, wells without growth factor are also included. After 24 h of incubation, BrdUrd labeling solution is added, and cells incubated an additional 24 h before fixation, blocking, and addition of peroxidase-labeled anti-BrdUrd antibody. Bound antibody is then detected using 3,3′ 5,5′-tetramethylbenzidine substrate[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1]
A porous Teflon chamber (volume, 0.5 mL) is filled with 0.8% w/v agar containing heparin (20 units/mL) with or without growth factor (3 μg/mL human VEGF, 2 μg/mL human PDGF) is implanted s.c. on the dorsal flank of C57/C6 mice. The mice are treated with Vatalanib (12.5, 25 or 50 mg/kg dihydrochloride p.o. once daily) or vehicle (water) starting 1 day before implantation of the chamber and continuing for 5 days after. At the end of treatment, the mice are killed, and the chambers are removed. The vascularized tissue growing around the chamber is carefully removed and weighed, and the blood content is assessed by measuring the hemoglobin content of the tissue[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]. Wood JM, et al. PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. Cancer Res. 2000, 60(8
[2]. Murakami M, et al. Tyrosine kinase inhibitor PTK/ZK enhances the antitumor effects of interferon-α/5-fluorouracil therapy for hepatocellular carcinoma cells. Ann Surg Oncol. 2011, 18(2), 589-596.
[3]. Wan J, et al. Local recurrence of small cell lung cancer following radiofrequency ablation is induced by HIF-1α expression in the transition zone. Oncol Rep. 2016 Mar;35(3):1297-308.
ML-9 (Free Base) is a selective and potent inhibitor of Akt kinase, inhibits myosin light-chain kinase (MLCK) and stromal interaction molecule 1 (STIM1) activity[3]. ML-9 (Free Base) inhibits inhibits MLCK, PKA and PKC activity with Ki values of 4, 32 and 54 μM, respectively[1]. ML-9 (Free Base) induces autophagy by stimulating autophagosome formation and inhibiting their degradation[3].
体外研究 (In Vitro)
ML9 (Free Base) (0-100 μM; 0-24 hours) has no reduction in cardiomyocyte viability, 50-100 μM significantly induces cell death[2]. ML9 (Free Base) (50 μM; 1-4 hours) significantly increases cleaved caspase-3 levels, decreased STIM1 protein levels by about 42%[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay[1]
Cell Line:
Neonatal rat ventricular myocytes (NRVM) cells
Concentration:
0, 10, 50 and 100 μM
Incubation Time:
0, 1, 4, 8 and 24 hours
Result:
Decreased cell viability at 50–100 μM concentration.
Apoptosis Analysis[1]
Cell Line:
Neonatal rat ventricular myocytes (NRVM) cells
Concentration:
50 μM
Incubation Time:
0, 1, 4, 8 hours
Result:
Induced cardiomyocyte death through necrosis and apoptosis.
分子量
324.83
Formula
C15H17ClN2O2S
CAS 号
110448-31-2
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]. Ito S, et al. ML-9, a myosin light chain kinase inhibitor, reduces intracellular Ca2+ concentration in guinea pig trachealis.Eur J Pharmacol. 2004 Feb 23;486(3):325-33.
[2]. Shaikh S, et al. The STIM1 inhibitor ML9 disrupts basal autophagy in cardiomyocytes by decreasing lysosome content.Toxicol In Vitro. 2018 Apr;48:121-127.
[3]. Kondratskyi A1, et al.Identification of ML-9 as a lysosomotropic agent targeting autophagy and cell death.Cell Death Dis. 2014 Apr 24;5:e1193.
AZD3839 free base is a potent and selective orally active, brain-permeable BACE1 inhibitor (Ki=26 nM). AZD3839 free base shows 14 and >1000-fold selectivity against BACE2 and cathepsin D, respectively. AZD3839 free base exhibits dose- and time-dependent lowering of plasma, brain, and cerebrospinal fluid Aβ levels in mouse, guinea pig, and non-human primate. AZD3839 free base can be used for the research of Alzheimer’s disease[1][2].
Clinical Trial
分子量
431.41
Formula
C24H16F3N5
CAS 号
1227163-84-9
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Sparve E et al. Prediction and modeling of effects on the QTc interval for clinical safety margin assessment, based on single-ascending-dose study data with AZD3839. J Pharmacol Exp Ther. 2014 Aug;350(2):469-78.
[2]. Jeppsson F et al. Discovery of AZD3839, a potent and selective BACE1 inhibitor clinical candidate for the treatment of Alzheimer disease. J Biol Chem. 2012 Nov 30;287(49):41245-57.
