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

被引：21

作者：

Okamoto, Mika ^{[1
]}

Hidaka, Akemi ^{[1
]}

Toyama, Masaaki ^{[1
]}

Hosoya, Takamitsu ^{[2
]}

Yamamoto, Makoto ^{[3
]}

Hagiwara, Masatoshi ^{[3
]}

Baba, Masanori ^{[1
]}

机构：

[1] Kagoshima Univ, Grad Sch Med & Dent Sci, Ctr Chron Viral Dis, Div Antiviral Chemotherapy, Kagoshima 8908544, Japan

[2] Tokyo Med & Dent Univ, Inst Biomat & Bioengn, Lab Chem Biosci, Tokyo 1010062, Japan

[3] Kyoto Univ, Grad Sch Med, Dept Anat & Dev Biol, Kyoto 6068501, Japan

来源：

ANTIVIRAL RESEARCH | 2015年 / 123卷

关键词：

HIV-1; Latent infection; CDK-9; Cyclin T1; Transcription inhibitor; HUMAN-IMMUNODEFICIENCY-VIRUS; CHRONICALLY INFECTED-CELLS; TYPE-1; REPLICATION; GENE-EXPRESSION; TRANSCRIPTION; POTENT;

D O I：

10.1016/j.antiviral.2015.08.012

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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 I (HIV-1) replication in chronically infected cells. Its 50% effective concentration was 1.4-2.1 mu M, irrespective of the cells used for antiviral assays, while its 50% cytotoxic concentration was >20 mu M, 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. (C) 2015 Elsevier B.V. All rights reserved.

引用

页码：1 / 4

页数：4

共 19 条

[1] Inhibition of human immunodeficiency virus type 1 replication in acutely and chronically infected cells by EM2487, a novel substance produced by a Streptomyces species [J].

Baba, M ;

Okamoto, M ;

Takeuchi, H .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1999, 43 (10) :2350-2355

[2]

Baba M, 1998, MOL PHARMACOL, V53, P1097

[3] Potent and selective inhibition of human immunodeficiency virus type 1 transcription by piperazinyloxoquinoline derivatives [J].

Baba, M ;

Okamoto, M ;

Makino, M ;

Kimura, Y ;

Ikeuchi, T ;

Sakaguchi, T ;

Okamoto, T .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1997, 41 (06) :1250-1255

[4] Inhibitors of HIV-1 gene expression and transcription [J].

Baba, M .

CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2004, 4 (09) :871-882

[5] Recent status of HIV-1 gene expression inhibitors [J].

Baba, Masanori .

ANTIVIRAL RESEARCH, 2006, 71 (2-3) :301-306

[6] OSCILLATION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS SURFACE-RECEPTOR IS REGULATED BY THE STATE OF VIRAL ACTIVATION IN A CD4+ CELL MODEL OF CHRONIC INFECTION [J].

BUTERA, ST ;

PEREZ, VL ;

WU, BY ;

NABEL, GJ ;

FOLKS, TM .

JOURNAL OF VIROLOGY, 1991, 65 (09) :4645-4653

[7] CYTOKINE-INDUCED EXPRESSION OF HIV-1 IN A CHRONICALLY INFECTED PROMONOCYTE CELL-LINE [J].

FOLKS, TM ;

JUSTEMENT, J ;

KINTER, A ;

DINARELLO, CA ;

FAUCI, AS .

SCIENCE, 1987, 238 (4828) :800-802

[8] TUMOR NECROSIS FACTOR-ALPHA INDUCES EXPRESSION OF HUMAN IMMUNODEFICIENCY VIRUS IN A CHRONICALLY INFECTED T-CELL CLONE [J].

FOLKS, TM ;

CLOUSE, KA ;

JUSTEMENT, J ;

RABSON, A ;

DUH, E ;

KEHRL, JH ;

FAUCI, AS .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (07) :2365-2368

[9] Acridone derivatives are selective inhibitors of HIV-1 replication in chronically infected cells [J].

Fujiwara, M ;

Okamoto, M ;

Watanabe, M ;

Machida, H ;

Shigeta, S ;

Konno, K ;

Yokota, T ;

Baba, M .

ANTIVIRAL RESEARCH, 1999, 43 (03) :189-199

[10] Identification of Novel Inhibitors of Human Immunodeficiency Virus Type 1 Replication by In Silico Screening Targeting Cyclin T1/Tat Interaction [J].

Hamasaki, Takayuki ;

Okamoto, Mika ;

Baba, Masanori .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2013, 57 (03) :1323-1331

← 1 2 →