title: Selective inhibition of HIV-1 replication by the CDK9 inhibitor FIT-039.
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.
authors: Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.
authors: Mika
authors: M
authors: Okamoto
authors: Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.
authors: Akemi
authors: A
authors: Hidaka
authors: Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.
authors: Masaaki
authors: M
authors: Toyama
authors: Laboratory of Chemical Bioscience, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo 101-0062, Japan.
authors: Takamitsu
authors: T
authors: Hosoya
authors: Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors: Makoto
authors: M
authors: Yamamoto
authors: Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors: Masatoshi
authors: M
authors: Hagiwara
authors: 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.
authors: Masanori
authors: M
authors: Baba
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D042863:Cyclin-Dependent Kinase 9 / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D011725:Pyridines / Q000378:metabolism* / Q000633:toxicity; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; C000595272:FIT-039; D011725:Pyridines; C467969:CDK9 protein, human; D042863:Cyclin-Dependent Kinase 9
keywords: CDK-9; Cyclin T1; HIV-1; Latent infection; Transcription inhibitor