AT-7519 diHCl

Description: AT-7519 diHCl is a novel and potent multi-CDK (cyclin-dependent kinase) inhibitor for Cdk1/cyclin B, Cdk2/Cyclin A, Cdk3/Cyclin E, Cdk4/Cyclin D1, Cdk5/p35, and Cdk6/Cyclin D3 with IC50s of 210, 47, 100, 13, 170, and< 10 nM for CDK1, CDK2, CDK4 to CDK6, and CDK9, respectively. AT7519 is an ATP competitive Cdk inhibitor but is inactive against all non-Cdk kinases with the exception of GSK3beta. AT7519 shows potent antiproliferative activity in a variety of human tumor cell lines such as SW620. AT7519 induces activation of GSK-3beta by down-regulating GSK-3beta phosphorylation, which also contributes to AT7519 induced apoptosis independent of the inhibition of transcription.

References:

1. SantoL, et al. AT7519, A novel small molecule multi-cyclin-dependent kinaseinhibitor, induces apoptosis in multiple myeloma via GSK-3betaactivation and RNA polymerase II inhibition. Oncogene. 2010 Apr22; 29(16):2325-36.

2. SquiresMS, et al. Biological characterization of AT7519, a small-moleculeinhibitor of cyclin-dependent kinases, in human tumor cell lines.Biological characterization of AT7519, a small-molecule inhibitor ofcyclin-dependent kinases, in human tumor cell lines.

3. SquiresMS, et al. AT7519, a cyclin-dependent kinase inhibitor, exerts itseffects by transcriptional inhibition in leukemia cell lines and patientsamples. Mol Cancer Ther. 2010 Apr; 9(4):920-8.

4. Komiyama T, Kihara H, Hirose K, Yoshimoto R, Shigematsu H. AT-1015, a novel serotonin2A receptor antagonist, improves resaturation of exercised ischemic muscle in hypercholesterolemic rabbits. J Vasc Surg. 2004 Mar; 39(3):661-7.

Related CAS #: 902135-91-5 (HCl) 844442-38-2 (free base)