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

Mika Okamoto; Akemi Hidaka; Masaaki Toyama; Takamitsu Hosoya; Makoto Yamamoto; Masatoshi Hagiwara; Masanori Baba

doi:10.1016/j.antiviral.2015.08.012

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

Antiviral Res. 2015 Nov:123:1-4. doi: 10.1016/j.antiviral.2015.08.012. Epub 2015 Aug 21.

Authors

Mika Okamoto¹, Akemi Hidaka¹, Masaaki Toyama¹, Takamitsu Hosoya², Makoto Yamamoto³, Masatoshi Hagiwara³, Masanori Baba⁴

Affiliations

¹ Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.
² Laboratory of Chemical Bioscience, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo 101-0062, Japan.
³ Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
⁴ Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan. Electronic address: m-baba@m2.kufm.kagoshima-u.ac.jp.

PMID: 26304705
DOI: 10.1016/j.antiviral.2015.08.012

Abstract

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 1.4-2.1μM, irrespective of the cells used for antiviral assays, while its 50% cytotoxic concentration was >20μM, 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.

Keywords: CDK-9; Cyclin T1; HIV-1; Latent infection; Transcription inhibitor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / metabolism*
Antiviral Agents / toxicity
Cell Survival / drug effects
Cyclin-Dependent Kinase 9 / antagonists & inhibitors*
HIV-1 / drug effects*
HIV-1 / physiology*
Humans
Microbial Sensitivity Tests
Pyridines / metabolism*
Pyridines / toxicity
Virus Replication / drug effects*

Substances

Antiviral Agents
FIT-039
Pyridines
CDK9 protein, human
Cyclin-Dependent Kinase 9