902135-91-5

AT7519 is an ATP-competitive inhibitor of cyclin-dependent kinases (Cdks) with IC₅₀ values of 210, 47, 100, 13, 170, and <10 nM for Cdk1, 2, 4, 5, 6, and 9, respectively. It is less potent against Cdk3 and Cdk7 and inactive against non-Cdk kinases save for GSK3β (IC₅₀ = 89 nM). AT7519 demonstrates antiproliferative activity against a wide variety of human tumor cell lines (IC₅₀s = 40-940 nM in vitro), inhibiting cell cycle progression and inducing apoptosis, and prevents tumor growth in human tumor xenograft models. AT7519 induces activation of GSK3β by down-regulating GSK3β phosphorylation, which contributes to AT7519-induced apoptosis.

4-(2,6-DichlorobenzoylaMino)-1H-pyrazole-3-carboxylic Acid Piperidin-4-ylaMide Monohydrochloride is used in the structure based design of a cyclin-dependant kinase CDK2 inhibitor.

CDK9/Cyclin T: 10 nM (IC₅₀); CDK5/p35: 13 nM (IC₅₀); cdk2/cyclin A: 47 nM (IC₅₀); Cdk4/cyclin D1: 100 nM (IC₅₀); cdk6/cyclin D3: 170 nM (IC₅₀); Cdk1/cyclin B: 210 nM (IC₅₀); CDK7/Cyclin H/MAT1: 2400 nM (IC₅₀); GSK3β: 89 nM (IC₅₀)

[1] MATTHEW S SQUIRES. Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines.[J]. Molecular Cancer Therapeutics, 2009, 8 2: 324-332. DOI: 10.1158/1535-7163.mct-08-0890
[2] L SANTO. AT7519, A novel small molecule multi-cyclin-dependent kinase inhibitor, induces apoptosis in multiple myeloma via GSK-3β activation and RNA polymerase II inhibition[J]. Oncogene, 2010, 29 16: 2325-2336. DOI: 10.1038/onc.2009.510