tcsc0017 AT7519

AT7519 as a potent inhibitor of CDKs, with IC₅₀s of 210, 47, 100, 13, 170, and <10 nM for CDK1, CDK2, CDK4 to CDK6, and CDK9, respectively.

IC50 & Target: IC50: <10 nM (CDK9), 13 nM (CDK5), 47 nM (CDK2), 100 nM (CDK4), 170 nM (CDK6), 210 nM (CDK1)^[2]

In Vitro: AT7519 (0-4 μM) results in dose-dependent cytotoxicity with IC₅₀s ranging from 0.5 to 2 μM in MM cells, and this induced cytotoxicity is associated with GSK-3β activation independent of transcriptional inhibition. AT7519 overcomes proliferative advantage conferred by cytokines and the protective effect of BMSC. AT7519 (0.5 μM) induces apoptosis of MM cells in a time-dependent manner. Moreover, AT7519 (0.5 μM) inhibits phosphorylation of RNA polymerase II CTD and partially inhibits RNA synthesis in MM.1S cells^[1]. AT7519 (250 nM) inhibits cell cycle progression in human tumor cell lines. AT7519 also induces apoptosis of human tumor cell lines^[2]. AT7519 (100-700 nM) induces apoptosis in leukemia cell lines. AT7519 also inhibits transcription in human tumor cell lines. Furthermore, AT7519 inhibits RNA polymerase II and reduces antiapoptotic protein levels^[3].

In Vivo: AT7519 inhibits tumor growth in a human MM xenograft mouse model^[1]. AT7519 (4.6 and 9.1 mg/kg/dose) inhibits the growth of early-stage HCT116 tumor xenografts. AT7519 (10 mg/kg, i.p.) also inhibits the target CDKs in HCT116 tumor-bearing BALB/c nude mice^[2].