GSK-3 Inhibitor XIII 是一种有效的 ATP 竞争性 GSK-3 抑制剂，Ki 为 24 nM。
GSK-3 Inhibitor XIII Chemical Structure
CAS No. : 404828-08-6
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
GSK-3 Inhibitor XIII is a potent and ATP-competitive GSK-3 inhibitor with a Ki of 24 nM[1][1][2].
分子量
305.38
Formula
C18H19N5
CAS 号
404828-08-6
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]. Albert C Pierce, et al. CH…O and CH…N hydrogen bonds in ligand design: a novel quinazolin-4-ylthiazol-2-ylamine protein kinase inhibitor. J Med Chem. 2005 Feb 24;48(4):1278-81.
[2]. Eduardo Cruz Moraes, et al. Kinase inhibitor profile for human nek1, nek6, and nek7 and analysis of the structural basis for inhibitor specificity. Molecules. 2015 Jan 13;20(1):1176-91.
GSK-3 Inhibitor XIII 是一种有效的 ATP 竞争性 GSK-3 抑制剂，Ki 为 24 nM。
GSK-3 Inhibitor XIII Chemical Structure
CAS No. : 404828-08-6
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
GSK-3 Inhibitor XIII is a potent and ATP-competitive GSK-3 inhibitor with a Ki of 24 nM[1][1][2].
分子量
305.38
Formula
C18H19N5
CAS 号
404828-08-6
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]. Albert C Pierce, et al. CH…O and CH…N hydrogen bonds in ligand design: a novel quinazolin-4-ylthiazol-2-ylamine protein kinase inhibitor. J Med Chem. 2005 Feb 24;48(4):1278-81.
[2]. Eduardo Cruz Moraes, et al. Kinase inhibitor profile for human nek1, nek6, and nek7 and analysis of the structural basis for inhibitor specificity. Molecules. 2015 Jan 13;20(1):1176-91.
GSK-3 Inhibitor XIII 是一种有效的 ATP 竞争性 GSK-3 抑制剂，Ki 为 24 nM。
GSK-3 Inhibitor XIII Chemical Structure
CAS No. : 404828-08-6
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
GSK-3 Inhibitor XIII is a potent and ATP-competitive GSK-3 inhibitor with a Ki of 24 nM[1][1][2].
分子量
305.38
Formula
C18H19N5
CAS 号
404828-08-6
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]. Albert C Pierce, et al. CH…O and CH…N hydrogen bonds in ligand design: a novel quinazolin-4-ylthiazol-2-ylamine protein kinase inhibitor. J Med Chem. 2005 Feb 24;48(4):1278-81.
[2]. Eduardo Cruz Moraes, et al. Kinase inhibitor profile for human nek1, nek6, and nek7 and analysis of the structural basis for inhibitor specificity. Molecules. 2015 Jan 13;20(1):1176-91.
Uprosertib hydrochloride (GSK2141795 hydrochloride) is a potent and selective pan-Akt inhibitor with IC50 values of 180/328/38 nM for Akt1/Akt2/Akt3, respectively.
IC50 & Target[1]
Akt1
180 nM (IC50)
Akt2
328 nM (IC50)
Akt3
38 nM (IC50)
CDK7
2100 nM (IC50)
ROCK1
1570 nM (IC50)
ROCK2
1850 nM (IC50)
体外研究 (In Vitro)
Uprosertib inhibits Akt1/2/3 with the Kd values of 16/49/5 nM, respectively. Uprosertib potently inhibits only the PKC family members PRKACA and PRKACB as well as the cGMP-dependent protein kinase PRKG1 aqpart from the Akts. Protein targets that bind Uprosertib in the lysate show a dose-dependent reduction in binding to the kinobeads, while proteins unaffected by the drug show no reduction in binding[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
465.71
Formula
C18H17Cl3F2N4O2
CAS 号
1047635-80-2
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]. Pachl F, et al. Characterization of a chemical affinity probe targeting Akt kinases. J Proteome Res. 2013 Aug 2;12(8):3792-800.
Kinase Assay [1]
For selectivity profiling experiments, the lysates (5 mg of total protein each) are preincubated with 0 (DMSO control), 2.5 nM, 25 nM, 250 nM, 2.5 μM or 25 μM free compound (GSK690693 or Uprosertib) on an end-over-end shaker for 45 min at 4°C. Subsequently, lysates are incubated with beads (coupled Akt probe or kinobeads) for 1 h at 4°C, for both qualitative and quantitative experiments. The beads are washed with 1×CP buffer and collected by centrifugation. Bound proteins are eluted with 2×NuPAGE LDS sample buffer, and eluates are reduced and alkylated by 50 mM dithiothreitol and 55 mM iodoacetamide.
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Pachl F, et al. Characterization of a chemical affinity probe targeting Akt kinases. J Proteome Res. 2013 Aug 2;12(8):3792-800.
Uprosertib hydrochloride (GSK2141795 hydrochloride) is a potent and selective pan-Akt inhibitor with IC50 values of 180/328/38 nM for Akt1/Akt2/Akt3, respectively.
IC50 & Target[1]
Akt1
180 nM (IC50)
Akt2
328 nM (IC50)
Akt3
38 nM (IC50)
CDK7
2100 nM (IC50)
ROCK1
1570 nM (IC50)
ROCK2
1850 nM (IC50)
体外研究 (In Vitro)
Uprosertib inhibits Akt1/2/3 with the Kd values of 16/49/5 nM, respectively. Uprosertib potently inhibits only the PKC family members PRKACA and PRKACB as well as the cGMP-dependent protein kinase PRKG1 aqpart from the Akts. Protein targets that bind Uprosertib in the lysate show a dose-dependent reduction in binding to the kinobeads, while proteins unaffected by the drug show no reduction in binding[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
465.71
Formula
C18H17Cl3F2N4O2
CAS 号
1047635-80-2
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]. Pachl F, et al. Characterization of a chemical affinity probe targeting Akt kinases. J Proteome Res. 2013 Aug 2;12(8):3792-800.
Kinase Assay [1]
For selectivity profiling experiments, the lysates (5 mg of total protein each) are preincubated with 0 (DMSO control), 2.5 nM, 25 nM, 250 nM, 2.5 μM or 25 μM free compound (GSK690693 or Uprosertib) on an end-over-end shaker for 45 min at 4°C. Subsequently, lysates are incubated with beads (coupled Akt probe or kinobeads) for 1 h at 4°C, for both qualitative and quantitative experiments. The beads are washed with 1×CP buffer and collected by centrifugation. Bound proteins are eluted with 2×NuPAGE LDS sample buffer, and eluates are reduced and alkylated by 50 mM dithiothreitol and 55 mM iodoacetamide.
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Pachl F, et al. Characterization of a chemical affinity probe targeting Akt kinases. J Proteome Res. 2013 Aug 2;12(8):3792-800.
Uprosertib hydrochloride (GSK2141795 hydrochloride) is a potent and selective pan-Akt inhibitor with IC50 values of 180/328/38 nM for Akt1/Akt2/Akt3, respectively.
IC50 & Target[1]
Akt1
180 nM (IC50)
Akt2
328 nM (IC50)
Akt3
38 nM (IC50)
CDK7
2100 nM (IC50)
ROCK1
1570 nM (IC50)
ROCK2
1850 nM (IC50)
体外研究 (In Vitro)
Uprosertib inhibits Akt1/2/3 with the Kd values of 16/49/5 nM, respectively. Uprosertib potently inhibits only the PKC family members PRKACA and PRKACB as well as the cGMP-dependent protein kinase PRKG1 aqpart from the Akts. Protein targets that bind Uprosertib in the lysate show a dose-dependent reduction in binding to the kinobeads, while proteins unaffected by the drug show no reduction in binding[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
465.71
Formula
C18H17Cl3F2N4O2
CAS 号
1047635-80-2
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]. Pachl F, et al. Characterization of a chemical affinity probe targeting Akt kinases. J Proteome Res. 2013 Aug 2;12(8):3792-800.
Kinase Assay [1]
For selectivity profiling experiments, the lysates (5 mg of total protein each) are preincubated with 0 (DMSO control), 2.5 nM, 25 nM, 250 nM, 2.5 μM or 25 μM free compound (GSK690693 or Uprosertib) on an end-over-end shaker for 45 min at 4°C. Subsequently, lysates are incubated with beads (coupled Akt probe or kinobeads) for 1 h at 4°C, for both qualitative and quantitative experiments. The beads are washed with 1×CP buffer and collected by centrifugation. Bound proteins are eluted with 2×NuPAGE LDS sample buffer, and eluates are reduced and alkylated by 50 mM dithiothreitol and 55 mM iodoacetamide.
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]. Pachl F, et al. Characterization of a chemical affinity probe targeting Akt kinases. J Proteome Res. 2013 Aug 2;12(8):3792-800.
GSK-J1 lithium salt is a potent inhibitor of H3K27me3/me2-demethylases JMJD3/KDM6B and UTX/KDM6A, with IC50 of 60 nM towards KDM6B.
IC50 & Target
IC50: 60 nM (KDM6B)[2]
体外研究 (In Vitro)
GSK-J1 is selective for H3K27 demethylases of the KDM6 subfamily and specifically binds to endogenous JMJD3. GSK-J1 inhibits TNF-α production by human primary macrophages in an H3K27-dependent manner[1]. GSK-J1 inhibits the demethylase activity of KDM5C with 8.5-fold increased potency compared with that of KDM5B at 1 mM α-ketoglutarate, with IC50 of 11 μM and 94 μM, respectively[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.
分子量
395.38
Formula
C22H22LiN5O2
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]. Kruidenier L, et al. A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature. 2012 Aug 16;488(7411):404-8.
[2]. Heinemann B, et al. Inhibition of demethylases by GSK-J1/J4. Nature. 2014 Oct 2;514(7520):E1-2
[3]. Horton JR, et al. Characterization of a Linked Jumonji Domain of the KDM5/JARID1 Family of Histone H3 Lysine 4 Demethylases. J Biol Chem. 2016 Feb 5;291(6):2631-46.
Kinase Assay [1]
Purified JmjD3 (1 μM) and UTX (3 μM) is incubated with 10 μM peptide [BiotinKAPRKQLATKAARK(me3 )SAPATGG] in 50 mM HEPES pH 7.5, 150 mM KCl, 50 μM (NH4)2SO4·FeSO4·H2O, 1 mM 2-oxoglutarate, and 2 mM ascorbate (JmjD3, 3 minutes at 25°C; UTX, 20 minutes at 25°C) with various concentration of the inhibitor (0, 0.005, 0.01, 0.02, 0.05, 0.1 μM). 10 mM EDTA is added to stop the reaction. The reaction is desalted by zip tip and spotted on a MALDI plate with α-cyano-4-hydroxycinnamic acid MALDI matrix. Samples are analysed on a MALDI-TOF R system.
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]. Kruidenier L, et al. A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature. 2012 Aug 16;488(7411):404-8.
[2]. Heinemann B, et al. Inhibition of demethylases by GSK-J1/J4. Nature. 2014 Oct 2;514(7520):E1-2
[3]. Horton JR, et al. Characterization of a Linked Jumonji Domain of the KDM5/JARID1 Family of Histone H3 Lysine 4 Demethylases. J Biol Chem. 2016 Feb 5;291(6):2631-46.
GSK2850163 hydrochloride is a novel inhibitor of inositol-requiring enzyme-1 alpha (IRE1α) which can inhibit IRE1α kinase activity and RNase activity with IC50s of 20 and 200 nM, respectively.
GSK2850163 hydrochloride is a novel inhibitor of inositol-requiring enzyme-1 alpha (IRE1α) which can inhibit IRE1α kinase activity and RNase activity with IC50s of 20 and 200 nM, respectively. The increased autophosphorylation of IRE1α can be reduced in a dose-dependent manner by GSK2850163 hydrochloride. Increasing concentrations of GSK2850163 hydrochloride are capable of reducing the increased XBP 1 transcriptional activity. Two additional kinases are weakly inhibited by GSK2850163 hydrochloride: Ron (IC50=4.4 μM) and FGFR1 V561M (IC50=17 μM)[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
482.87
Formula
C24H30Cl3N3O
CAS 号
2319838-09-8
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]. Nestor O. Concha, et al. Long-Range Inhibitor-Induced Conformational Regulation of Human IRE1α Endoribonuclease Activity. Molecular Pharmacology December 2015, 88 (6) 1011-1023.
Kinase Assay [1]
In the ADP-Glo assay, GSK2850163 hydrochloride’s potency toward pIRE1α kinase activity is measured as its inhibition of an intrinsic, slowing ATP hydrolysis activity. One hundred nanoliters of dimethylsulfoxide solution of GSK2850163 hydrochloride at various concentrations is added into a 384-well plate. The reaction is carried out with 5 nM pIRE1α and 60 mM ATP in 10 mL of 50 mM Hepes buffer, pH 7.5, containing 30 mM NaCl, 10 mM MgCl2, 1 mM DTT, 0.02% Chaps, and 0.01 mg/mL bovine serum albumin. The reaction is stopped after 2 hours by adding 5 mL of ADP-Glo reagent I, which also depletes the remaining ATP. Following 1-hour incubation, 5 mL of ADP-Glo reagent II is added into the reaction, which converts the ADP product into ATP to serve as the substrate for the coupled luciferin/luciferase reaction. After 30 minutes, the plate is read on a microplate imager[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 Assay [1]
PANC-1 cells are seeded into six-well plates at a density of 5.0×103 cells/well in RPMI 1640 media containing 10% FBS. Cells are cotransfected with a pGL3-5x unfolded protein response element (UPRE)-luciferase reporter containing five repetitions of the XBP-1 DNA binding site and pRL-SV40 using the FuGENE6 transfection reagent. Forty-eight hours later, cells are treated with 2.5 mg/mL tunicamycin for 1 hour, followed by GSK2850163 hydrochloride treatment for 16 hours. Luciferase expression is measured using Dual-Glo Luciferase Assay kit and normalized to Renilla expression levels[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]. Nestor O. Concha, et al. Long-Range Inhibitor-Induced Conformational Regulation of Human IRE1α Endoribonuclease Activity. Molecular Pharmacology December 2015, 88 (6) 1011-1023.
GSK3186899 (DDD-853651) is an inhibitor of cdc-2-related kinase 12 (CRK12), with an EC50 of 1.4 μM for L. donovani in an intra-macrophage assay.
IC50 & Target
CRK12[1].
体外研究 (In Vitro)
GSK3186899 (Compound 7) is active against L. donovani in an intra-macrophage assay with an EC50 value of 1.4 μM, and shows good selectivity against mammalian THP-1 host cells (EC50 value>50 μM). This is not as potent as reported data for amphotericin B (EC50 value of 0.07 μM in the intra-macrophage assay), but is comparable to the clinically used drugs miltefosine and paromomycin (EC50 values of 0.9 μM and 6.6 μM, respectively). GSK3186899 is also active in cidal axenic amastigote assay (EC50 value of 0.1 μM). At a concentration of 0.2 μM, GSK3186899 is cytocidal at 96 h; increasing the concentration to 1.8 μM reduced this time to 48 h. GSK3186899 demonstrates a less than 10-fold variation in potency against a panel of Leishmania-derived lines. GSK3186899 is also more active in a panel of Leishmania lines using human peripheral blood mononuclear cells as the host 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.
体内研究 (In Vivo)
In the mouse model of infection, GSK3186899 demonstrates comparable activity to the front-line drug miltefosine, reducing parasite levels by 99% when dosed orally twice a day for 10 days at 25 mg/kg. The efficacy of treatment is dependent on dose, frequency, and duration (10 days better than 5). The non-clinical safety data for GSK3186899 suggests a suitable therapeutic window for progression into regulatory preclinical studies. Non-GLP preclinical assessment of cardiovascular effects and genotoxicity does not reveal any issues that would prevent further development. In addition, there are no notable adverse effects in a rat seven-day repeat-dose oral toxicity study with respect to clinical chemistry and histopathology at all doses tested. Both the in vivo efficacy and safety profile of GSK3186899 support progression to definitive safety studies[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
491.53
Formula
C19H28F3N7O3S
CAS 号
1972617-87-0
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]. Wyllie S, et al. Cyclin-dependent kinase 12 is a drug target for visceral leishmaniasis. Nature. 2018 Aug;560(7717):192-197.
GSK2194069 is a potent and specific inhibitor of the β-ketoacyl reductase (KR) activity of hFAS with an IC50 of 7.7 ± 4.1 nM in an assay detecting released CoA. IC50 value: Target: hFAS inhibitor
分子量
428.48
Formula
C25H24N4O3
CAS 号
1332331-08-4
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Hardwicke MA, et al. A human fatty acid synthase inhibitor binds β-ketoacyl reductase in the keto-substrate site. Nat Chem Biol. 2014 Sep;10(9):774-9.
Trametinib (GSK1120212; JTP-74057) is an orally active MEK inhibitor that inhibits MEK1 and MEK2 with IC50s of about 2 nM. Trametinib activates autophagy and induces apoptosis[1][2].
IC50 & Target[1]
MEK1
2 nM (IC50)
MEK2
2 nM (IC50)
体外研究 (In Vitro)
Trametinib (GSK1120212;JTP-74057) (0.1-100 nM) blocks tumor necrosis factor-α and interleukin-6 production from peripheral blood mononuclear cells (PBMCs). Trametinib (JTP-74057) inhibits the growth of 9 out of 10 human colorectal cancer cell lines, and they shows cell-cycle arrest at the G1 phase after drug tratment[1]. The combination of GSK2118436 and Trametinib (GSK1120212) effectively inhibits cell growth, decreases ERK phosphorylation, decreases cyclin D1 protein, and increases p27(kip1) protein in the resistant clones[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)
Adjuvant-induced arthritis (AIA) and type II collageninduced arthritis (CIA) development are suppressed almost completely by 0.1 mg/kg of Trametinib (GSK1120212; JTP-74057) or 10 mg/kg of HWA486[1]. Trametinib (0.3 mg/kg, 1 mg/kg, p.o.) is effective in inhibiting the HT-29 xenograft growth in a nude mouse xenograft model[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.
Clinical Trial
分子量
615.39
Formula
C26H23FIN5O4
CAS 号
871700-17-3
中文名称
曲美替尼
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
溶解性数据
In Vitro:
DMSO : 25 mg/mL (40.62 mM; ultrasonic and warming and heat to 60°C)
[1]. Yamaguchi T, et al. Suppressive effect of an orally active MEK1/2 inhibitor in two different animal models for rheumatoid arthritis: a comparison with HWA486. Inflamm Res, 2012, 61(5), 445-454.
[2]. Yamaguchi T, et al. Antitumor activities of JTP-74057 (GSK1120212), a novel MEK1/2 inhibitor, on colorectal cancer cell lines in vitro and in vivo. Int J Oncol, 2011, 39(1), 23-31.
[3]. Abe H, et al. Discovery of a Highly Potent and Selective MEK Inhibitor: GSK1120212 (JTP-74057 DMSO Solvate). ACS Med Chem Lett. 2011 Feb 28;2(4):320-4.
[4]. Liu H, et al. Identifying and Targeting Sporadic Oncogenic Genetic Aberrations in Mouse Models of Triple Negative Breast Cancer. Cancer Discov. 2018 Mar;8(3):354-369.
[5]. Lai J, et al. Elimination of melanoma by sortase A-generated TCR-like antibody-drug conjugates (TL-ADCs) targeting intracellular melanoma antigen MART-1. Biomaterials. 2018 Sep;178:158-169.
Kinase Assay [2]
The nonphosphorylated myelin basic protein (MBP) is coated onto an ELISA plate, and the active form of B-Raf/c-Raf is mixed with unphosphorylated MEK1/MEK2 and ERK2 in 10 µM ATP and 12.5 mM MgCl2 containing MOPS buffer in the presence of various concentrations of Trametinib (JTP-74057). The phosphorylation of MBP is detected by the anti-phosphoMBP antibody. Kinase inhibitory activities against a total of 99 kinases are tested at 10 µM ATP[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 Assay [2]
Cells are treated with various concentrations of Trametinib (JTP-74057) in 100 mm dishes for 3 or 4 days. Both floating and adherent cells are collected and fixed with 70% ethanol. After washing with PBS, the cells are suspended in 100 µL/mL RNase and 25 µL/mL Propidium iodide (PI) and incubated at 37°C for 30 min in the dark. The DNA content of each single cell is determined using the flow cytometer Cytomics FC500 or Guava EasyCyte plus[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 Administration [2]
Mice[2] Female BALB/c-nu/nu mice are used. On day 0, HT-29 cells or COLO205 cells suspended in ice-cold HBSS (-) are inoculated subcutaneously into the right flank of the mice at 5×106 cells/100 µL/site or 1×106 cells/100 µL/site, respectively. The acetic acid-solvated form of Trametinib (JTP-74057, 0.3 mg/kg, 1 mg/kg) is dissolved in 10% Cremophor EL-10% PEG400 and is administered orally once daily for 14 days from the day when the mean tumor volume reached 100 mm3. The tumor length [L(mm)] and width [W(mm)] are measured using a microgauge twice a week after commencement of dosing, and the tumor volume is calculated using the following formula: tumor volume (mm3)=L×W×W/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.
参考文献
[1]. Yamaguchi T, et al. Suppressive effect of an orally active MEK1/2 inhibitor in two different animal models for rheumatoid arthritis: a comparison with HWA486. Inflamm Res, 2012, 61(5), 445-454.
[2]. Yamaguchi T, et al. Antitumor activities of JTP-74057 (GSK1120212), a novel MEK1/2 inhibitor, on colorectal cancer cell lines in vitro and in vivo. Int J Oncol, 2011, 39(1), 23-31.
[3]. Abe H, et al. Discovery of a Highly Potent and Selective MEK Inhibitor: GSK1120212 (JTP-74057 DMSO Solvate). ACS Med Chem Lett. 2011 Feb 28;2(4):320-4.
[4]. Liu H, et al. Identifying and Targeting Sporadic Oncogenic Genetic Aberrations in Mouse Models of Triple Negative Breast Cancer. Cancer Discov. 2018 Mar;8(3):354-369.
[5]. Lai J, et al. Elimination of melanoma by sortase A-generated TCR-like antibody-drug conjugates (TL-ADCs) targeting intracellular melanoma antigen MART-1. Biomaterials. 2018 Sep;178:158-169.
GSK-3685032 是一种非时间依赖、非共价、可逆的 DNMT1 选择性抑制剂，IC50=0.036 μM。GSK-3685032 诱导 DNA 甲基化丧失、转录激活和癌细胞生长抑制。
GSK-3685032 Chemical Structure
CAS No. : 2170137-61-6
规格
价格
是否有货
数量
5 mg
￥3500
In-stock
10 mg
￥5800
In-stock
25 mg
￥11000
In-stock
50 mg
询价
100 mg
询价
* Please select Quantity before adding items.
GSK-3685032 相关产品
•相关化合物库:
Bioactive Compound Library Plus
Epigenetics Compound Library
Anti-Cancer Compound Library
Reprogramming Compound Library
Anti-Blood Cancer Compound Library
Transcription Factor Targeted Library
生物活性
GSK-3685032 is a non-time-dependent, noncovalently, first-in-class reversible DNMT1-selective inhibitor, with an IC50 of 0.036 μM. GSK-3685032 induces robust loss of DNA methylation, transcriptional activation, and cancer cell growth inhibition[1].
IC50 & Target
DNMT1[1]
体外研究 (In Vitro)
GSK-3685032 (6 days) has cell growth inhibition of majority cancer cell lines, with a median growth IC50 value of 0.64 μM[1]. GSK-3685032 (0.1-1000 nM, 1-6 days) exhibits growth inhibition after 3 days, with decreasing growth IC50 throughout a 6 d time course[1]. GSK3685032 (10-10000 nM, day 4) dose-dependently increases the immune-related gene transcription[1]. GSK3685032 (3.2-10,000 nM, 2 days) inhibits DNMT1 protein expression[1]. GSK3685032 induces DNA hypomethylation and gene activation[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.
[1]. Pappalardi MB, et al. Discovery of a first-in-class reversible DNMT1-selective inhibitor with improved tolerability and efficacy in acute myeloid leukemia. Nat Cancer. 2021;2(10):1002-1017.
GSK126 (GSK2816126A) is a potent, highly selective inhibitor of EZH2 methyltransferase with an IC50 of 9.9 nM[1].
IC50 & Target[1]
EZH2
9.9 nM (IC50)
体外研究 (In Vitro)
GSK126 potently inhibits both wild-type and mutant EZH2 methyltransferase activity with similar potencies (Ki=0.5-3 nM) independent of substrate used, and is competitive with S-adenosyl-methionine (SAM) and non-competitive with peptide substrates. GSK126 is highly selective against other methyltransferases and multiple other protein classes (EZH1, IC50=680 nM)[1]. Treatment of three SCLC cell lines with GSK126, induces growth inhibition. SCLC cell lines (Lu130, H209, and DMS53) are treated with 0.5, 2, and 8 μM GSK126, and growth curve is analyzed by WST-8 assay. Inhibition of cellular growth by GSK126 treatment is observed at 8 μM in all the three cell lines, while Lu130 and H209 are more sensitive to GSK126, even at lower doses[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)
GSK126 is administered intraperitoneally at a dose volume of 0.2 mL per 20 g body weight in female beige SCID mice. GSK126 effectively inhibits the proliferation of EZH2 mutant DLBCL cell lines and markedly inhibits the growth of EZH2 mutant DLBCL xenografts in 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
526.67
Formula
C31H38N6O2
CAS 号
1346574-57-9
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. McCabe MT, et al. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature. 2012 Dec 6;492(7427):108-12.
[2]. Sato T, et al. PRC2 overexpression and PRC2-target gene repression relating to poorer prognosis in small cell lung cancer. Sci Rep. 2013 May 29;3:1911.
Kinase Assay [1]
The five-member PRC2 complex (Flag-EZH2, EED, SUZ12, AEBP2, RbAp48) containing either wild-type or mutant (A677G, Y641N, Y641C, Y641H, Y641S or Y641F) EZH2 is prepared. GSK126 is dissolved in DMSO and tested at concentrations of 0.6 nM to 300 nM with a final DMSO concentration of 2.5%. In contrast to wild-type EZH2 which prefers H3K27me0 as a substrate in vitro, EZH2 Y641 mutants prefer H3K27me2 and have little activity with H3K27me0 or H3K27me1. The A677G mutant is distinct from both the wild-type and Y641 mutant forms of EZH2 in that it efficiently methylates H3K27me0, H3K27me1, and H3K27me2; therefore, histone H3 peptides (residues 21-44; 10 μM final) with either K27me0 (wild type, A677G EZH2), K27me1 (A677G EZH2), or K27me2 (A677G, Y641N, Y641C, Y641H, Y641S and Y641F EZH2) are used as methyltransferase substrates. GSK126 is added to plates followed by addition of 6 nM EZH2 complex and peptide. As the potency of GSK126 is at or near the tight binding limit of an assay run at [SAM]=Km, IC50 values are measured at a high concentration of the competitive substrate SAM relative to its Km (7.5 μM SAM where the SAM Km is 0.3 μM)[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 Assay [2]
JUB– and PTRF-introduced DMS53 cells are seeded at density of 1×103 cells/well in 96-well plate, and cellular growth is analyzed using WST-8 kit at 12, 36, 60, and 84 h. Cellular growth of Lu130, H209, and DMS53 with treatment by DZNep or GSK126 is also analyzed using WST-8 kit. DZNep is dissolved in PBS at 5 mM, and cells are cultured at the final concentration of 5 μM. GSK126 is dissolved in DMSO at 10 mM, and cells are cultured at 0.5, 2, and 8 μM[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 Administration [1]
Mice[1] GSK126 or vehicle is administered intraperitoneally at a dose volume of 0.2 mL per 20 g body weight. Pfeiffer or KARPAS-422 cells (1×107) in 100% Matrigel are implanted subcutaneously in female beige SCID mice. Tumors are measured with calipers, and block randomized according to tumour size into treatment groups. For efficacy studies, 10 mice are randomized in each treatment group before the initiation of dosing and GSK126 treatment is initiated once the tumour volumes are approximately 200 mm3 in the Pfeiffer and KARPAS-422 studies and 500 mm3 in the KARPAS-422 intermittent dosing study. Mice are weighed and tumors measured with calipers twice weekly. Two-tailed t-tests are conducted assuming two samples of equal variance.
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]. McCabe MT, et al. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature. 2012 Dec 6;492(7427):108-12.
[2]. Sato T, et al. PRC2 overexpression and PRC2-target gene repression relating to poorer prognosis in small cell lung cancer. Sci Rep. 2013 May 29;3:1911.
GSK2983559 active metabolite 是 GSK2983559 的活性代谢物。GSK2983559 active metabolite 是一种受体相互作用蛋白-2 (RIP2) 激酶抑制剂，详细信息请参考专利 WO/2014043446 A1 中的化合物 example 1。
GSK2983559 active metabolite Chemical Structure
CAS No. : 1423186-80-4
规格
价格
是否有货
数量
10 mM * 1 mL in DMSO
￥3531
In-stock
1 mg
￥1400
In-stock
5 mg
￥3500
In-stock
10 mg
￥5000
In-stock
50 mg
询价
100 mg
询价
* Please select Quantity before adding items.
GSK2983559 active metabolite 相关产品
•相关化合物库:
Clinical Compound Library Plus
Bioactive Compound Library Plus
Apoptosis Compound Library
Kinase Inhibitor Library
NF-κB Signaling Compound Library
Anti-Cancer Compound Library
Clinical Compound Library
生物活性
GSK2983559 active metabolite is an active metabolite of GSK2983559. GSK2983559 active metabolite is a receptor interacting protein-2 (RIP2) kinase inhibitor extracted from patent WO/2014043446 A1, compound example 1.
IC50 & Target
RIP2 Kinase[1]
体外研究 (In Vitro)
GSK2983559 active metabolite is a novel prodrug of a quinazolyl amine that inhibits RIP2 kinase. Receptor interacting protein-2 (RIP2) kinase, which is also referred to as CARD3, RICK, CARDIAK, or RIPK2, is a TKL family serine/threonine protein kinase involved in innate immune signaling. RIP2 kinase is composed of an N-terminal kinase domain and a C-terminal caspase-recruitment domain (CARD) linked via an intermediate (IM) region. The CARD domain of RIP2 kinase mediates interaction with other CARD-containing proteins, such as NODI and NOD2. NODI and NOD2 are cytoplasmic receptors which play a key role in innate immune surveillance. They recognize both gram positive and gram negative bacterial pathogens and are activated by specific peptidoglycan motifs, diaminopimelic acid (i.e., DAP) and muramyl dipeptide[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
458.55
Formula
C21H22N4O4S2
CAS 号
1423186-80-4
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Linda N. Casillas, et al. Prodrugs of amino quinazoline kinase inhibitor. PCT Int. Appl. (2014), WO 2014043446 A1 20140320.
Animal Administration [1]
Rats[1] Rats are orally pre-dosed with RIP2 kinase inhibitor 1, at a dose of 2 mg/kg (8 rats) and with Prednisolone (8 rats, used as a positive control), followed by dosing with L18-MDP (50 μg/rat) 0.25 h/min after pre-dosing. Combined cytokine levels (IL8, TNFa, IL6 and IL-Ιβ) in whole blood samples taken from the rats in this study are measured using an antibody based detection. The combined cytokine response is calculated as the averaged response for the 4 cytokines measured relative to the response observed in the vehicle-treated mice, and are depicted as the mean±standard error of the mean (n=8 rats/group).
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]. Linda N. Casillas, et al. Prodrugs of amino quinazoline kinase inhibitor. PCT Int. Appl. (2014), WO 2014043446 A1 20140320.
[1]. Axten JM, et al. Discovery of 7-methyl-5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (GSK2606414), a potent and selective first-in-class inhibitor of protein kinase R (PKR)-like endoplasmic reticulu
[2]. Zhang M, et al. Inhibiting the Plasmodium eIF2α Kinase PK4 Prevents Artemisinin-Induced Latency. Cell Host Microbe. 2017 Dec 13;22(6):766-776.e4.
Animal Administration [1]
Exponentially growing BxPC3 tumor cells (10×106 cells/mouse) from cell culture are implanted subcutaneously into the right flank of female nude mice. Sixteen days after implantation, mice with -200 mm3 tumors are randomized into various treatment groups (n=8 mice/group). Animals are orally treated with vehicle (0.5% hydoxypropylmethylcellulose, 0.1% Tween 80 in water, pH 4.8), compound at 50 or 150 mg/kg, b.i.d. for 21 days. Tumor volume is measured twice weekly with calipers and calculated. Results are represented as percent inhibition on completion of dosing, which is 100[1-(average growth of drug-treated population)/(average growth of vehicle-treated control population)]. Statistical analysis is performed using a two-tailed t test.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Axten JM, et al. Discovery of 7-methyl-5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (GSK2606414), a potent and selective first-in-class inhibitor of protein kinase R (PKR)-like endoplasmic reticulu
[2]. Zhang M, et al. Inhibiting the Plasmodium eIF2α Kinase PK4 Prevents Artemisinin-Induced Latency. Cell Host Microbe. 2017 Dec 13;22(6):766-776.e4.
