Integrase inhibitor
Integrase inhibitors 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 first integrase inhibitor approved by the U.S. Food and Drug Administration (FDA) was raltegravir (brand name Isentress), approved on October 12, 2007. 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.
[edit] Drugs under development
- Elvitegravir (GS 9137 or JTK-303), licensed by Gilead Sciences from Japan Tobacco, is currently undergoing Phase 3 clinical trials.[2] GS 9137 is a low-molecular-weight, highly selective integrase inhibitor that shares the core structure of quinolone antibiotics.[3]
- MK-2048, a second generation integrase inhibitor, that appears to have a duration of action up to 4 times longer than raltegravir.
[edit] 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. http://content.nejm.org/cgi/content/abstract/359/4/339.
- ^ Gilead Press Release Phase III Clinical Trial of Elvitegravir July 22, 2008
- ^ AIDSinfo - HIV/AIDS Drug Information - GS 9137 (elvitegravir)
[edit] 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. http://www.ingentaconnect.com/content/apl/eid/2006/00000015/00000012/art00004?token=00461400d664264f65263a3d4f58762f467c405847447b23442f5f31256f5b20655d3b.
- IntegraseBookFull PDF
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