- Integrase inhibitor
Integrase inhibitors are a class of
antiretroviral drugdesigned to block the action of integrase, a viral enzyme that inserts the viral genome into the DNAof 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 HIVinfection, but they could be applied to other retroviruses.
The first integrase inhibitor approved by the US Food and Drug Administration (FDA) was
Raltegravir(brand name Isentress), approved on October 12, 2007. Research results published in the New England Journal of Medicineon July 24, 2008, concluded that "raltegravir plus optimized background therapy provided better viral suppression than optimized background therapy alone for at least 48 weeks." [cite journal |author=Steigbigel RT, Cooper DA, Kumar PN, "et al" |title=Raltegravir with optimized background therapy for resistant HIV-1 infection |journal=N. Engl. J. Med. |volume=359 |issue=4 |pages=339–54 |year=2008 |month=Jul |pmid=18650512 |doi=10.1056/NEJMoa0708975 |url=http://content.nejm.org/cgi/content/abstract/359/4/339]
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 therapyfor patients whose virus has mutated and acquired resistance to other drugs.
Drugs under development
Elvitegravir(GS 9137 or JTK-303), licensed by Gilead Sciencesfrom Japan Tobacco, is currently undergoing Phase 2 clinical trials. GS 9137 is a low-molecular-weight, highly selective integrase inhibitor that shares the core structure of quinoloneantibiotics. [ [http://aidsinfo.nih.gov/DrugsNew/DrugDetailT.aspx?int_id=421 AIDSinfo - HIV/AIDS Drug Information - GS 9137 (elvitegravir) ] ]
* [http://www.natap.org/2005/EACS/eacs_3.htm MK-0518, the first Integrase Inhibitor for HIV]
* [http://www.thebody.com/thebody/newdrugs.html HIV Antiretroviral Agents in Development]
* [http://aidsinfo.nih.gov/DrugsNew/DrugDetailT.aspx?int_id=421 GS 9137 (elvitegravir) factsheet from NIH]
*cite journal |author=Savarino A |title=A historical sketch of the discovery and development of HIV-1 integrase inhibitors |journal=Expert Opin Investig Drugs |volume=15 |issue=12 |pages=1507–22 |year=2006 |month=Dec |pmid=17107277 |doi=10.1517/135437220.127.116.117 |url=http://www.ingentaconnect.com/content/apl/eid/2006/00000015/00000012/art00004?token=00461400d664264f65263a3d4f58762f467c405847447b23442f5f31256f5b20655d3b
* [http://discover.nci.nih.gov/pommier/IntegraseBookFull.pdf IntegraseBookFull PDF]
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