Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.16 (HIV-1 protease)
 2,107 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cage dimeric N-benzyl 4-aryl-1,4-dihydropyridine H17 is a moderate inhibitor of HIV-1 protease. As representative of an innovative and promising class of nonpeptidic HIV-1 protease inhibitors H17 was selected for the characterization of the biochemical profile of the cage dimers concerning metabolic and toxic aspects. In the first bioanalytical evaluation of H17 on Hep G2 monolayers no phase-I metabolites were found and the extent of conjugation on phase-II of biotransformation was poor due to steric hindrance of the hydroxymethylene groups. H17 was found to be nearly non-toxic. A slight noticeable influence on cell proliferation, however, did not result from apoptotic activities. Thus, first biochemical evaluation of H17 practically suggests no decrease of an in-vivo bioavailability by metabolization.
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PMID:First bioanalytical evaluation of nonpeptidic cage dimeric HIV-1 protease inhibitor N-benzyl 4-aryl-1,4-dihydropyridine H17: biotransformation and toxicity on Hep G2 cells. 1067 87

Cyclic ureas form a perspective class of non-peptidic HIV-1 protease inhibitors with major bioavailability problems. Low absorption rates of DMP 323 as one of the first representatives led to investigations whether transport efflux pump P-glycoprotein (P-gp) within the intestine may be partly responsible for the low absorption rates. DMP 323 proved to be a P-gp substrate in competition studies with P-gp inhibitor ritonavir and H17 as a representative of another class of non-peptidic HIV-1 protease inhibitors. Intestinal DMP 323 absorption was mainly increased under co-application of both ritonavir and H17. DMP 323 used as a membrane efflux pump inhibitor itself showed little affinities to P-gp compared to H17 as strong P-gp inhibitor. So P-gp proved to play a decisive role in the low intestinal absorption of the cyclic urea representative DMP 323.
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PMID:P-glycoprotein effects of cyclic urea HIV protease inhibitor DMP 323 in competitional absorption studies. 1704 92