WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 573173
Description: JSH-150 is a potent CDK9 inhibitor. JSH-150 exhibited an IC50 of 1 nM against CDK9 kinase in the biochemical assay and achieved around 300-10000-fold selectivity over other CDK kinase family members. In addition, it also displayed high selectivity over other 468 kinases/mutants (KINOMEscan S score(1) = 0.01). JSH-150displayed potent antiproliferative effects against melanoma, neuroblastoma, hepatoma, colon cancer, lung cancer as well as leukemia cell lines. It could dose-dependently inhibit the phosphorylation of RNA Pol II, suppress the expression of MCL-1 and c-Myc, arrest the cell cycle and induce the apoptosis in the leukemia cells.
MedKoo Cat#: 573173
Chemical Formula: C24H33ClN6O2S
Exact Mass: 504.2074
Molecular Weight: 505.08
Elemental Analysis: C, 57.07; H, 6.59; Cl, 7.02; N, 16.64; O, 6.34; S, 6.35
Synonym: JSH-150; JSH 150; JSH150;
IUPAC/Chemical Name: 4-(((4-(5-chloro-2-((4-((2-methoxyethyl)amino)cyclohexyl)amino)pyridin-4-yl)thiazol-2-yl)amino)methyl)tetrahydro-2H-pyran-4-carbonitrile
InChi Key: XSDZPPRQLIZLDG-WEBLMRDCSA-N
InChi Code: InChI=1S/C24H33ClN6O2S/c1-32-11-8-27-17-2-4-18(5-3-17)30-22-12-19(20(25)13-28-22)21-14-34-23(31-21)29-16-24(15-26)6-9-33-10-7-24/h12-14,17-18,27H,2-11,16H2,1H3,(H,28,30)(H,29,31)/t17?,18-
SMILES Code: COCCNC1CC[C@H](NC2=NC=C(Cl)C(C3=CSC(NCC4(C#N)CCOCC4)=N3)=C2)CC1
In the MV4-11 cell-inoculated xenograft mouse model, 10 mg/kg dosage of 40 could almost completely suppress the tumor progression. The high selectivity and good in vivo PK/PD profile suggested that JSH-150 would be a good pharmacological tool to study CDK9-mediated physiology and pathology as well as a potential drug candidate for leukemia and other cancers.
1: Wang B, Wu J, Wu Y, Chen C, Zou F, Wang A, Wu H, Hu Z, Jiang Z, Liu Q, Wang W, Zhang Y, Liu F, Zhao M, Hu J, Huang T, Ge J, Wang L, Ren T, Wang Y, Liu J, Liu Q. Discovery of 4-(((4-(5-chloro-2-(((1s,4s)-4-((2-methoxyethyl)amino)cyclohexyl)amino)pyridin-4- yl)thiazol-2-yl)amino)methyl)tetrahydro-2H-pyran-4-carbonitrile (JSH-150) as a novel highly selective and potent CDK9 kinase inhibitor. Eur J Med Chem. 2018 Oct 5;158:896-916. doi: 10.1016/j.ejmech.2018.09.025. Epub 2018 Sep 13. PubMed PMID: 30253346.