View source for Protease inhibitors

:''For natural protease inhibitors, please see [[protease inhibitor (biology)]]''

'''Protease inhibitors''' (PIs) are a class of [[medication]] used to treat or prevent [[infection]] by [[virus]]es, including [[HIV]] and [[Hepatitis C]]. PIs prevent viral replication by inhibiting the activity of [[HIV-1 protease]], an [[enzyme]] used by the viruses to cleave nascent [[protein]]s for final assembly of new [[virons]].

Protease inhibitors have been developed or are presently undergoing testing for treating various viruses:
* [[HIV]]/[[AIDS]]: [[antiretroviral drug|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 [[antibiotic]]s, of the development of drug-resistant mutated viruses. To reduce this risk it is common to use together different drugs aimed at different targets.

==Antiretrovirals==
Protease inhibitors were the second class of [[antiretroviral drug]]s developed. In all cases, patents remain in force until 2010 or beyond.

{| class="wikitable"
| '''Name''' || '''Trade name''' || '''Company''' || '''Patent''' || '''Notes'''
 |- 
 | [[Saquinavir]]  || Fortovase, Invirase || [[Hoffmann–La Roche]] || {{US patent|5196438}} || It was the first protease inhibitor approved by the [[Food and Drug Administration|FDA]] ([[December 6]], [[1995]]).
 |- 
 | [[Ritonavir]] || Norvir || [[Abbott Laboratories]] || {{US patent|5541206}} || -
 |- 
 | [[Indinavir]]  || Crixivan  || [[Merck & Co.]] || {{US patent|5413999}} || -
 |- 
 | [[Nelfinavir]]  || Viracept  || [[Japan Tobacco]] || {{US patent|5484926}} || -
 |- 
 | [[Amprenavir]]  || Agenerase  || [[GlaxoSmithKline]] || {{US patent|5585397}} || 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  Production was discontinued by the manufacturer [[December 31]], [[2004]], as it has been superseded by fosamprenavir.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]]  || Kaletra || [[Abbott Laboratories|Abbott]] || - || Is only marketed as a combination, with [[ritonavir]]. 
 |- 
 | [[Atazanavir]]  || Reyataz  || - || - || -
 |- 
 | [[Fosamprenavir]] || Lexiva || [[GlaxoSmithKline]] || - || 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  || [[Boehringer-Ingelheim]] || - || Also known as tipranavir disodium 
 |- 
 | [[Darunavir]]  || Prezista  || [[Tibotec]] || - ||  It was approved by the [[Food and Drug Administration]] (FDA) on [[June 23]], [[2006]]. Several ongoing [[Clinical trial#Phase III| phase III]] trials are showing a high efficiency for the PREZISTA/[[ritonavir|rtv]] combination being superior to the [[lopinavir]]/[[ritonavir|rtv]] combination for first-line therapy<ref>Darunavir-ritonavir more effective than Lopinavir-ritonavir in HIV infected, treatment-experienced patients,The Lancet, Volume 370, Number 9581, 07 July 2007, http://www.thelancet.com/journals/lancet/issue?volume=370&issue=9581</ref>. Darunavir is  the first drug in a long time that didn't come with a price increase. It  [[leapfrogging|leapfrogged]] two other approved drugs of its type, and is matching the price of a third <ref>Liz Highleyman, Patient Advocates Commend Pricing of New PI Darunavir, http://www.hivandhepatitis.com/recent/2006/ad1/063006_a.html</ref><ref>[Darunavir - first molecule to treat drug-resistant HIV, http://www.news-medical.net/?id=19211]</ref><ref>[Retaining Efficacy Against Evasive HIV, http://pubs.acs.org/cen/news/84/i34/8434drugdesign.html]</ref>.

|}

==References==
<references />
* A [http://inventors.about.com/library/inventors/bl_protease_inhibitors.htm brief history] of the development of protease inhibitors by Hoffman La Roche, Abbott, and Merck
{{Antivirals}}
[[Category:Antivirals]]
[[Category:Antiretroviral drugs]]

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