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a substance that retards or stops an activity

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抑制する人(物) / 化学反応抑制剤

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/06 21:53:47」(JST)

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Integrase inhibitors, also known as integrase strand transfer inhibitors (INSTIs), are a class of antiretroviral drug designed to block the action of integrase, a viral enzyme that inserts the viral genome into the DNA of the host cell. Since integration is a vital step in retroviral replication, blocking it can halt further spread of the virus. Integrase inhibitors were initially developed for the treatment of HIV infection, but they could be applied to other retroviruses.

The discovery and development of integrase inhibitors led to the first integrase inhibitor approval by the U.S. Food and Drug Administration (FDA) on October 12, 2007, for raltegravir (brand name Isentress). Research results published in the New England Journal of Medicine on July 24, 2008, concluded that "raltegravir plus optimized background therapy provided better viral suppression than optimized background therapy alone for at least 48 weeks."^[1]

Since integrase inhibitors target a distinct step in the retroviral life cycle, they may be taken in combination with other types of HIV drugs to minimize adaptation by the virus. They are also useful in salvage therapy for patients whose virus has mutated and acquired resistance to other drugs.

Drugs in use and under development

Currently in use

Elvitegravir (GS 9137 or JTK-303), licensed by Gilead Sciences from Japan Tobacco, after undergoing Phase 3 clinical trials,^[2] was approved by the U.S. Food and Drug Administration on August 27, 2012 for use in adult patients starting HIV treatment for the first time as part of the fixed dose combination Stribild. Elvitegravir is a low-molecular-weight, highly selective integrase inhibitor that shares the core structure of quinolone antibiotics.^[3]
dolutegravir, brand name Tivicay, licensed by ViiV Healthcare, was approved by the FDA in 2013 and has recently gained European approval in January 2014. Dolutegravir is marketed as 50mg tablets as a once or twice daily add on to concurrent HAART therapy.
raltegravir, brand name Isentress.

Under development

MK-2048, a second generation integrase inhibitor, that appears to have a duration of action up to four times longer than raltegravir.

References

^ Steigbigel RT, Cooper DA, Kumar PN et al. (July 2008). "Raltegravir with optimized background therapy for resistant HIV-1 infection". N. Engl. J. Med. 359 (4): 339–54. doi:10.1056/NEJMoa0708975. PMID 18650512.
^ Gilead Press Release Phase III Clinical Trial of Elvitegravir July 22, 2008
^ AIDSinfo - HIV/AIDS Drug Information - GS 9137 (elvitegravir)

External links

MK-0518, the first Integrase Inhibitor for HIV
HIV Antiretroviral Agents in Development
GS 9137 (elvitegravir) factsheet from NIH
Savarino A (December 2006). "A historical sketch of the discovery and development of HIV-1 integrase inhibitors". Expert Opin Investig Drugs 15 (12): 1507–22. doi:10.1517/13543784.15.12.1507. PMID 17107277.
IntegraseBookFull PDF

UpToDate Contents

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1. インテグラーゼ阻害剤の薬理学 pharmacology of integrase inhibitors
2. HIV抗レトロウイルス療法に関する臨床試験：インテグラーゼ阻害剤 clinical trials of hiv antiretroviral therapy integrase inhibitors
3. HIV薬剤耐性検査の解釈についての手引 primer on interpretation of hiv drug resistance testing
4. 妊娠時の抗レトロウイルス剤：侵入阻害剤およびインテグラーゼ阻害剤 antiretroviral medications in pregnancy entry and integrase inhibitors
5. 治療経験のある薬剤耐性HIV感染患者の評価 evaluation of the treatment experienced patient with drug resistant hiv infection

English Journal

Insight into the Inhibitory Mechanism and Binding Mode Between D77 and HIV-1 Integrase by Molecular Modeling Methods.

Li P, Tan JJ, Liu M, Zhang XY, Chen WZ, Wang CX.SourceCollege of Life Sciences and Bioengineering, Beijing University of Technology, Beijing 100124, China. cxwang@bjut.edu.cn.
Journal of biomolecular structure & dynamics.J Biomol Struct Dyn.2011 Oct;29(2):311-23.
Integrase is an essential enzyme in the life cycle of Human immunoficiency virus type 1 (HIV-1) and also an important target for designing integrase inhibitors. In this paper, the binding modes between the wild type integrase core domain (ICD) and the W131A mutant ICD with the benzoic acid derivativ
PMID 21875151

Japanese Journal

High Performance Liquid Chromatography Using UV Detection for the Simultaneous Quantification of the New Non-nucleoside Reverse Transcriptase Inhibitor Etravirine (TMC-125), and 4 Protease Inhibitors in Human Plasma

Hirano Atsushi,Takahashi Masaaki,Kinoshita Eri,Shibata Masaaki,Nomura Toshiharu,Yokomaku Yoshiyuki,Hamaguchi Motohiro,Sugiura Wataru
Biological & Pharmaceutical Bulletin 33(8), 1426-1429, 2010
… Thus, ETV has been used in combination with ritonavir-boosted protease inhibitor (PI) and integrase inhibitor for therapy-experienced HIV-1-infected patients. …
NAID 130000300371