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)

Emivirine (EMV), formerly known as MKC-442, is 6-benzyl-1-(ethoxymethyl)-5-isopropyl-uracil, a novel nonnucleoside reverse transcriptase inhibitor that displays potent and selective anti-human immunodeficiency virus type 1 (HIV-1) activity in vivo. EMV showed little or no toxicity towards human mitochondria or human bone marrow progenitor cells. Pharmacokinetics were linear for both rats and monkeys, and oral absorption was 68% in rats. Whole-body autoradiography showed widespread distribution in tissue 30 min after rats were given an oral dose of [(14)C]EMV at 10 mg/kg of body weight. In rats given an oral dose of 250 mg/kg, there were equal levels of EMV in the plasma and the brain. In vitro experiments using liver microsomes demonstrated that the metabolism of EMV by human microsomes is approximately a third of that encountered with rat and monkey microsomes. In 1-month, 3-month, and chronic toxicology experiments (6 months with rats and 1 year with cynomolgus monkeys), toxicity was limited to readily reversible effects on the kidney consisting of vacuolation of kidney tubular epithelial cells and mild increases in blood urea nitrogen. Liver weights increased at the higher doses in rats and monkeys and were attributed to the induction of drug-metabolizing enzymes. EMV tested negative for genotoxic activity, and except for decreased feed consumption at the high dose (160 mg/kg/day), with resultant decreases in maternal and fetal body weights, EMV produced no adverse effects in a complete range of reproductive toxicology experiments performed on rats and rabbits. These results support the clinical development of EMV as a treatment for HIV-1 infection in adult and pediatric patient populations.
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PMID:Safety assessment, in vitro and in vivo, and pharmacokinetics of emivirine, a potent and selective nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1. 1060 32

Emivirine (MKC-442) structurally is a nucleoside analog (NRTI) molecule, but it functions as a non-nucleoside reverse transcriptase inhibitor (NNRTI). It inhibits HIV replication by binding to the reverse transcriptase viral enzyme. The drug is classified as an NNRTI and is the only anti-HIV drug to demonstrate this cross-class dichotomy. Results of early phase I and phase II clinical trials shows the drug is well tolerated in monotherapy and that it suppresses by 96 percent. Genotypic and phenotypic analyses of the drug were presented at this year's ICAAC, and results from two trials shows that viruses containing NNRTI mutations occuring with emivirine therapy remain active against one or more of the approved NNRTIs in about 43 percent of cases. A study of emivirine in pregnant women is also discussed. Triangle Pharmaceuticals remains optimistic about the drug, but results do not confirm yet that emivirine will preserve the option of switching to another NNRTI later. Emivirine will probably be used in protease-sparing regimens. The trial results will probably delay approval of emivirine until further studies are completed.
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PMID:Emivirine: an NRTI that functions as an NNRTI. 1136 64

Information on how HIV-positive women can maintain a healthy pregnancy, presented at the 1999 Conference on Women and HIV, is summarized. Topics include receiving quality care, the safety of Emivirine, and a comparison of statistics on pregnancy outcomes in infected and non-infected women. A brief summary of maternal factors related to transmission is presented. The impact of recreational drug use, as well as domestic abuse on mother and fetus, are also discussed.
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PMID:Healthy mom, healthy baby: pregnancy and prenatal issues. 1136 19

Updates are provided for new anti-HIV drugs currently in development. ABT-378, Tipranavir, and DMP-450 are among the new protease inhibitors discussed. Drugs from other classes that are discussed include emivirine (Coactinon, formerly MKC-442), FTC (emtricitabine, Coviracil), adefovir (Preveon), and pentafuside (T-20). A small study has found that women using Ritonavir (Norvir) may be at a greater risk for anemia (a decrease in red blood cells), caused by excessive menstrual bleeding or hypermenorrhea. New formulations of Ritonavir and ddI (Didanosine, Videx) are described.
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PMID:New anti-HIV drugs in development. 1136 65

Emivirine (EMV) is a non-nucleoside reverse transcriptase inhibitor currently undergoing Phase III clinical trials in HIV-1-infected patients. In this study, the anti-HIV-1 activity of EMV in combination with two nucleoside reverse transcriptase inhibitors was examined in cell cultures. The combinations EMV plus stavudine (d4T) plus lamivudine (3TC) and EMV plus d4T plus didanosine (ddI) synergistically inhibited HIV-1 replication in MT-4 cells. Although not statistically significant, EMV plus d4T plus 3TC appeared to be more synergistic than EMV plus d4T plus ddI. Synergism was also observed with any two-drug combinations, such as EMV plus d4T, EMV plus 3TC, EMV plus ddI, d4T plus 3TC, or d4T plus ddI. The three-drug combinations completely suppressed HIV-1 replication for at least 40 days after virus infection. Except for d4T, virus emerged in the presence of every compound alone or some combinations at lower concentrations. Susceptibility tests of the breakthrough viruses to each compound showed that the viruses obtained in the presence of EMV alone and 3TC alone were significantly less susceptible to EMV and 3TC, respectively. These viruses had specific amino acid mutations in their reverse transcriptase.
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PMID:Three-drug combinations of emivirine and nucleoside reverse transcriptase inhibitors in vitro: long-term culture of HIV-1-infected cells and breakthrough viruses. 1295 24

Furoannelated analogues 1-alkoxymethyl-7-phenyl-5, 7-dihydro-1H-furo[3, 4-d]-pyrimidine-2, 4-diones of Emivirine (3a, b) were synthesized from the primary alcohols 1-alkoxymethyl-6-benzyl-5-hydroxymethyl-1H-pyrimidine-2, 4-dione (5a, b) using a radical ring closure reaction with Pb(OAc)(4). These analogues are conformationally restricted in order to fix the aromatic substituent of Emivirine in nearly the same position as it is in the case when the complex of Emivirine is bound to HIV-1 RT. However, the anti HIV-1 activities of 3a, b were considerably lower than those of the lead Emivirine.
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PMID:Synthesis of furoannelated analogues of Emivirine (MKC-442). 1503 59

1-Substiuted 6-(3-cyanobenzoyl) and [(3-cyanophenyl)fluoromethyl]-5-ethyl-uracils were synthesized and evaluated in cell-based assays against HIV-1 wild-type and its clinically relevant non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant mutants. Some of the synthesized compounds showed activity against HIV-1 wild-type in the same range as Emivirine (MKC-442). 3-{[3-(Allyloxymethyl)-5-ethyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl]fluoromethyl}-benzonitrile 11b showed moderate activity against the Y181C HIV-1 mutant strain.
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PMID:Synthesis and anti-HIV-1 activity of 1-substiuted 6-(3-cyanobenzoyl) and [(3-cyanophenyl)fluoromethyl]-5-ethyl-uracils. 1963 80