Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent results from human clinical trials have established the critical role of HIV protease inhibitors in the treatment of acquired immune-deficiency syndrome (AIDS). However, the emergence of viral resistance, demanding treatment protocols, and adverse side effects have exposed the urgent need for a second generation of HIV protease inhibitors. The continued exploration of our hydroxylaminepentanamide (HAPA) transition-state isostere series of HIV protease inhibitors, which initially resulted in the identification of Crixivan (indinavir sulfate, MK-639, L-735,524), has now yielded MK-944a (L-756,423). This compound is potent, is selective, and competitively inhibits HIV-1 PR with a K(i) value of 0.049 nM. It stops the spread of the HIV(IIIb)-infected MT4 lymphoid cells at 25.0-50.0 nM, even in the presence of alpha(1) acid glycoprotein, human serum albumin, normal human serum, or fetal bovine serum. MK-944a has a longer half-life in several animal models (rats, dogs, and monkeys) than indinavir sulfate and is currently in advanced human clinical trials.
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PMID:Identification of MK-944a: a second clinical candidate from the hydroxylaminepentanamide isostere series of HIV protease inhibitors. 1097 86

Protease inhibitors are the most well-known type of HIV drug, and five of them are currently approved by the Federal government. This first-generation of protease inhibitors includes Crixivan, Norvir, Fortovase, Viracept, and Agenerase. These drugs, while effective, do not eliminate HIV from the body, nor do they work well for everyone. A second-generation of protease inhibitors is in development, that researchers hope will be easier to take, and better at eliminating HIV. Included in this group are L-756,423, Tipranavir, BMS232632, and ABT-378(r). The benefits and potential drawbacks of each drug are briefly described. People who are considering switching treatments should consult their doctors about the possibility of entering a clinical trial.
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PMID:The younger generation. 1136 65

Protease inhibitors block the protease enzyme of HIV-1. When new viral particles break off from an infected cell, protease cuts long protein strands into the parts needed to assemble a mature virus. When protease is blocked, the new viral particles cannot mature. Protease inhibitors being tested in humans include Atazanavir, GW433908, L-756,423, Mozenavir(DMP-450), Tipranavir and more. Several firms are trying to develop a new type of protease inhibitor that will be the more favorable pharmacokinetic and resistance profiles compared with currently available drugs. We cannot expect that every one of the drugs listed in this paper will be successfully developed. However, it is likely that significant clinical advancements can be made with those that are proven to be active and safe for patients in need.
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PMID:[New HIV-1 protease inhibitors in development]. 1196 88