A Cdk9 inhibitor
FIT-039 is an inhibitor of cyclin-dependent kinase 9 (Cdk9; IC50 = 5.8 ?M for Cdk9/cyclin T1).1 It is selective for Cdk9/cyclin T1 over Cdk4/cyclin D3 at 30 ?M and Cdk2/cyclin A2, Cdk2/cyclin E1, Cdk5/p25, Cdk6/cyclin D3, and Cdk7/cyclin/MAT1 at 10 ?M but also inhibits GSK3α, GSK3β, PKN1, haspin, p70S6K, DYRK1B, DYRK3, and IRR at 10 ?M. FIT-039 inhibits DNA replication of herpes simplex virus 1 (HSV-1) in HeLa cells (IC50 = 0.69 ?M). Topical application of FIT-039 (1.25-10% w/w) reduces skin lesions and improves survival in HSV-1-infected mice. FIT-039 (300 mg/kg) also reduces tumor growth in a human papillomavirus (HPV) type 16-positive Ca Ski cervical cancer mouse xenograft model.2
1.Yamamoto, M., Onogi, H., Kii, I., et al.CDK9 inhibitor FIT-039 prevents replication of multiple DNA virusesJ. Clin. Invest.124(8)3479-3488(2014) 2.Ajiro, M., Sakai, H., Onogi, H., et al.CDK9 inhibitor FIT-039 suppresses viral oncogenes E6 and E7 and has a therapeutic effect on HPV-induced neoplasiaClin. Cancer Res.24(18)4518-4528(2018)
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