FIT-039 is a selective and ATP-competitive, orally active inhibitor of CDK9( IC50 : 5.8 μM;CDK9/cyclin T1). FIT-039 inhibits replication of HSV-1 (IC50 of 0.69 μM), HSV-2, human adenovirus, and human CMV. FIT-039 is a promising antiviral agent for inhibiting drug-resistant HSVs and other DNA viruses.

HSV1:0.69 μM, CDK9-CyclinT1:5.8 μM

FIT-039通过抑制HPV复制和表达E6和E7病毒癌基因，恢复HPV+宫颈癌细胞中的肿瘤抑制因子p53和pRb。在组织型筏培养的CIN模型中，FIT-039显示出治疗效果，抑制了HPV18引起的异型增生/增殖并降低了病毒负荷。FIT-039还能抑制HPV16+的宫颈癌异种移植瘤生长，但对HPV-宫颈癌异种移植瘤则无显著影响，且没有任何显著的不良反应。FIT-039的安全性和药代动力学已经通过系统和局部途径确认[1]。

Examined FIT-039 for its effect on HPV gene expression in HPV+ cervical cancer cells.?Primary keratinocytes monolayer and organotypic raft culture models were used to evaluate HPV viral replication and cervical intraepithelial neoplasia (CIN) phenotypes.?Preclinical pharmacokinetics and toxicity tests for FIT-039 were also conducted.?Finally, the anti-HPV effect of FIT-039 was further examined in vivo, using HPV+ cervical cancer xenografts[1]