CDK inhibitor E9

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

CDK抑制剂E9是一种新型CDK抑制剂，可以克服ABC介导的THZ1耐药性，作为CDK9的有效非共价抑制剂和CDK12的共价抑制剂。

CDK inhibitor E9 is a novel CDK inhibitor that can overcomes ABC-mediated resistance of THZ1, functions as a potent, non-covalent inhibitor of CDK9 and a covalent inhibitor of CDK12; does not serve as a substrate for either ABCB1 or ABCG2, while avoiding ABC transporter-mediated efflux; decreases the phosphorylated and total RNAPII in THZ1R NB and lung cancer cells (IC50=8-40 nM), accompanied by decreased MYC and MCL1 expression, exerts its cytotoxic effects through covalent modification of cysteine 1039 of CDK12.

CDK12-IN-E9 (E9; 10 nM-10 μM; 72 hours; Kelly, LAN5, SK-N-BE2, PC-9, NCI-H82 and NCI-H3122 cells) treatment shows potent antiproliferative activity in THZ1R NB and lung cancer cells, with IC50 values ranging from 8 to 40 nM.CDK12-IN-E9 (E9; 0-3000 nM; 6 hours; Kelly, PC-9, and NCI-H82 cells) treatment leads to a dose-dependent decrease in phosphorylated and total RNAPII in THZ1r NB and lung cancer models, accompanied by decreased MYC and MCL1 expression.CDK12-IN-E9 also results in increased PARP cleavage, and an increase in the subGI population in THZ1r lung cancer cells, while in NB cells, more of a G2/M arrest is seen after a 24-hr exposure to CDK12-IN-E9. Cell Proliferation Assay Cell Line:Kelly, LAN5, SK-N-BE2, PC-9, NCI-H82 and NCI-H3122 cells Concentration:10 nM-10 μM Incubation Time:72 hours Result:Showed potent antiproliferative activity in THZ1R NB and lung cancer cells, with IC50 values ranging from 8 to 40 nM.Western Blot Analysis Cell Line:Kelly, PC-9, and NCI-H82 cells Concentration:0 nM, 30 nM, 100 nM, 300 nM, 1000 nM, 3000 nM Incubation Time:6 hours Result:Led to a dose-dependent decrease in phosphorylated and total RNAPII in THZ1r NB and lung cancer models.

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E9

Angiogenesis

CDK

CDK

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2020052-55-3

434.544

C24H30N6O2

>98% (HPLC)

In Vitro:?DMSO : 125 mg/mL (287.67 mM)

C=CC(NC1=CC=CC(NC2=CC(N3[C@H](CCO)CCCC3)=NC4=C(CC)C=NN24)=C1)=O

(S)-N-(3-((3-ethyl-5-(2-(2-hydroxyethyl)piperidin-1-yl)pyrazolo[1,5-a]pyrimidin-7-yl)amino)phenyl)acrylamide

(-20℃)

With Ice Pack

≥ 2 years