YKL-5-124

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

YKL-5-124 是一种新型有效、选择性、共价 CDK7 抑制剂 (IC50=53.5 nM)，抑制 CDK7/CycH/MAT1 酶活性，IC50 为 9.7 nM。

YKL-5-124 is a novel potent, selective, and covalent CDK7 inhibitor (IC50=53.5 nM), inhibits CDK7/CycH/MAT1 enzymatic activity with IC50 of 9.7 nM; displays biochemical and cellular selectivity for CDK7 over structurally related kinases CDK12/13, and no significant activity against CDK2 and CDK9 (IC50>1 uM); targets and forms a covalent bond with CDK7- cysteine 312 (C312); inhibition of CDK7 by YKL-5-124 elicits a transcriptional signature distinct from that of THZ1, shows no discernible effect on RNA Pol II CTD phosphorylation; recapitulate THZ1-mediated effects on gene expression and CTD phosphorylation when combined with CDK12/13 inhibitor THZ531.

YKL-5-124 (0-2000 nM; 72 hours; HAP1 cells) treatment causes a dose-dependent increase in G1- and G2/M-phase cells and a corresponding loss of S-phase cells.YKL-5-124 (0-2000 nM; 24 hours; HAP1 WT cells) treatment inhibits CDK1 T-loop phosphorylation, and to a lesser extent CDK2 T-loop phosphorylation in a concentration-dependent fashion.Treatment of cells with YKL-5-124 as a competitor at a concentration of about 30 nM blocks pull-down of CDK7-cyclin H but has no effect on the pull-down of cyclin K-CDK12/13 in HAP1 cells. Treatment with 100 nM YKL-5-124 reduces CDK7-cyclin H binding to bioTHZ1 by >50% at 30 min.Cell Cycle AnalysisCell Line:HAP1 cells Concentration:0 nM, 0.2 nM, 0.7 nM, 2 nM, 6.3 nM, 20 nM, 60 nM, 200 nM, 633.3 nM, 2000 nM Incubation Time:72 hours Result:Caused a dose-dependent increase in G1- and G2/M-phase cells and a corresponding loss of S-phase cells.Western Blot Analysis Cell Line:HAP1 cells Concentration:0 nM, 125 nM, 250 nM, 500 nM, 1000 nM, 2000 nM Incubation Time:24 hours Result:Inhibited CDK1 T-loop phosphorylation, and to a lesser extent CDK2 T-loop phosphorylation in a concentration-dependent fashion.

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Angiogenesis

CDK

CDK

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1957203-01-8

515.618

C28H33N7O3

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (193.95 mM)

O=C(N(C1)C(C)(C)C2=C1C(NC(C3=CC=C(NC(C=C)=O)C=C3)=O)=NN2)N[C@@H](C4=CC=CC=C4)CN(C)C

(S)-3-(4-acrylamidobenzamido)-N-(2-(dimethylamino)-1-phenylethyl)-6,6-dimethyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxamide

(-20℃)

With Ice Pack

≥ 2 years