Protease inhibitor (pharmacology)
From Wikipedia, the free encyclopedia
- For natural protease inhibitors, please see protease inhibitor (biology)
Protease inhibitors (PIs) are a class of medication used to treat or prevent infection by viruses, including HIV and Hepatitis C. PIs prevent viral replication by inhibiting the activity of protease, an enzyme used by the viruses to cleave nascent proteins for final assembly of new virons.
Protease inhibitors have been developed or are presently undergoing testing for treating various viruses:
- HIV/AIDS: antiretroviral protease inhibitors (saquinavir, ritonavir, indinavir, nelfinavir etc.)
- Hepatitis C: experimental agents: BILN 2061, VX 950.
Given the specificity of the target of these drugs there is the risk, as in antibiotics, of the development of drug-resistant mutated viruses. To reduce this risk it is common to use together different drugs aimed at different targets.
[edit] Antiretrovirals
Protease inhibitors were the second class of antiretroviral drugs developed. In all cases, patents remain in force until 2010 or beyond.
| Name | Trade name | Company | Patent | Notes |
| Saquinavir | Fortovase, Invirase | Hoffmann–La Roche | U.S. Patent 5,196,438 | - |
| Ritonavir | Norvir | Abbott Laboratories | U.S. Patent 5,541,206 | - |
| Indinavir | Crixivan | Merck & Co. | U.S. Patent 5,413,999 | - |
| Nelfinavir | Viracept | Japan Tobacco | U.S. Patent 5,484,926 | - |
| Amprenavir | Agenerase | GlaxoSmithKline | U.S. Patent 5,585,397 | The FDA approved it April 15, 1999, making it the sixteenth FDA-approved antiretroviral. It was the first protease inhibitor approved for twice-a-day dosing instead of needing to be taken every eight hours. The convenient dosing came at a price, as the dose required is 1,200mg, delivered in eight very large gel capsules. Production was discontinued by the manufacturer December 31, 2004, as it has been superseded by fosamprenavir. |
| Lopinavir | - | - | - | Is only marketed as a combination, with ritonavir. |
| Atazanavir | Reyataz | - | - | - |
| Fosamprenavir | Lexiva | - | - | Is a pro-drug of amprenavir. The FDA approved it October 20, 2003. The human body metabolizes fosamprenavir in order to form amprenavir, which is the active ingredient. That metabolization increases the duration that amprenavir is available, making fosamprenavir a slow-release version of amprenavir and thus reduces the number of pills required versus standard amprenavir. |
| Tipranavir | Aptivus | - | - | Also known as tipranavir disodium |
[edit] References
A brief history of the development of protease inhibitors by Hoffman La Roche, Abbott, and Merck: http://inventors.about.com/library/inventors/bl_protease_inhibitors.htm
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| Anti-herpesvirus | Aciclovir, Cidofovir, Docosanol, Famciclovir, Fomivirsen, Foscarnet, Ganciclovir, Idoxuridine, Penciclovir, Trifluridine, Tromantadine, Valaciclovir, Valganciclovir, Vidarabine |
| Anti-influenza agents | Amantadine, Arbidol, Oseltamivir, Peramivir, Rimantadine, Zanamivir |
| Antiretrovirals: NRTIs | Abacavir, Didanosine, Emtricitabine, Lamivudine, Stavudine, Zalcitabine, Zidovudine |
| Antiretrovirals: NtRTIs | Tenofovir |
| Antiretrovirals: NNRTIs | Efavirenz, Delavirdine, Nevirapine, Loviride |
| Antiretrovirals: PIs | Amprenavir, Atazanavir, Darunavir, Fosamprenavir, Indinavir, Lopinavir, Nelfinavir, Ritonavir, Saquinavir, Tipranavir |
| Antiretrovirals: Fusion inhibitors | Enfuvirtide |
| Other antiviral agents | Adefovir, Fomivirsen, Imiquimod, Inosine, Interferon, Podophyllotoxin, Ribavirin, Viramidine |
