Selective inhibition of HIV-1 replication by the CDK9 inhibitor FIT-039

• FIT-039 is a novel CDK9 inhibitor with potent antiviral activity against a broad spectrum of DNA viruses.
• FIT-039 selectively inhibits HIV-1 p24 antigen production in chronically infected cells with an EC50 values of 1.4–2.1 μM.
• The mechanism of action appears to be the inhibition of HIV-1 gene expression from proviral DNA.

FIT-039 has recently been identified as a novel cyclin-dependent kinase 9 inhibitor with potent antiviral activity against a broad spectrum of DNA viruses, such as herpes simplex virus type 1 (HSV-1) and human cytomegaloviruses. In this study, FIT-039 was examined for its inhibitory effect on human immunodeficiency virus type 1 (HIV-1) replication in chronically infected cells. Its 50% effective concentration was 1.4–2.1 μM, irrespective of the cells used for antiviral assays, while its 50% cytotoxic concentration was >20 μM, indicating that FIT-039 is a selective inhibitor of HIV-1 replication. FIT-039 also inhibited HIV-1 RNA expression in a dose-dependent fashion. Since previous studies demonstrated that FIT-039 exhibited antiviral efficacy without noticeable adverse effects in HSV-1-infected mice, the compound should be further investigated for its clinical potential against HIV-1 infection.