Integrase inhibitor
Encyclopedia
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."
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.
Discovery and development of integrase inhibitors
The first human immunodeficiency virus case was reported in the 1980s. Many drugs have been discovered to treat the disease but mutations in the virus and resistance to the drugs make development difficult. Integrase is a viral enzyme that integrates retroviral DNA into the host cell genome....
are a class of antiretroviral drug
Antiretroviral drug
Antiretroviral drugs are medications for the treatment of infection by retroviruses, primarily HIV. When several such drugs, typically three or four, are taken in combination, the approach is known as Highly Active Antiretroviral Therapy, or HAART...
designed to block the action of integrase
Integrase
Retroviral integrase is an enzyme produced by a retrovirus that enables its genetic material to be integrated into the DNA of the infected cell...
, a viral enzyme that inserts the viral genome into the DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
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
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
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
New England Journal of Medicine
The New England Journal of Medicine is an English-language peer-reviewed medical journal published by the Massachusetts Medical Society. It describes itself as the oldest continuously published medical journal in the world.-History:...
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."
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
Salvage therapy
Salvage therapy is a form of treatment given after an ailment does not respond to standard treatment. The most common diseases that require salvage therapy are HIV and various tumors...
for patients whose virus has mutated and acquired resistance to other drugs.
Drugs under development
- ElvitegravirElvitegravirElvitegravir is an investigational new drug for the treatment of HIV infection. It acts as an integrase inhibitor. It is undergoing Phase III clinical trial conducted by the pharmaceutical company Gilead Sciences, which licensed EVG from Japan Tobacco in March 2008.According to the results of...
(GS 9137 or JTK-303), licensed by Gilead SciencesGilead SciencesGilead Sciences is a biopharmaceutical company that discovers, develops and commercializes therapeutics. For many years since the company was founded, the company concentrated primarily on antiviral drugs to treat patients infected with HIV, hepatitis B or influenza. In 2006, Gilead acquired two...
from Japan TobaccoJapan Tobacco, abbreviated JT, is a cigarette manufacturing company. It is part of the Nikkei 225 index. In 2009 the company was listed at number 312 on the Fortune 500 list. The company is headquartered in Toranomon, Minato, Tokyo. The international headquarters are in Geneva, Switzerland.-History:The company...
, is currently undergoing Phase 3 clinical trials. GS 9137 is a low-molecular-weight, highly selective integrase inhibitor that shares the core structure of quinoloneQuinoloneThe quinolones are a family of synthetic broad-spectrum antibiotics. The term quinolone refers to potent synthetic chemotherapeutic antibacterials....
antibiotics. - MK-2048MK-2048MK-2048 is a second generation integrase inhibitor, intended to be used against HIV infection. It is superior to the first available integrase inhibitor, raltegravir, in that it inhibits the HIV enzyme integrase 4 times longer. It is being investigated for use as part of pre-exposure prophylaxis...
, a second generation integrase inhibitor, that appears to have a duration of action up to 4 times longer than raltegravir.