Abstract: In order to understand the basis for this resilience at the molecular level and to help the design of further-improved anti-AIDS drugs, we have determined crystal structures of efavirenz and nevirapine with wild-type RT and the clinically important K103N mutant.
Calanolides, the naturally occurring anti-HIV agents.
PMID: 19649847
2000
Current opinion in drug discovery & development
Abstract: Moreover, when challenged with viruses containing Y181C and K103N dual mutations, calanolide compounds remain active.
Abstract: Of particular interest is the use of calanolide in the treatment of patients who have failed other NNRTI therapy and developed the Y181C mutation or the Y181C/K103N dual mutations.
The P236L delavirdine-resistant human immunodeficiency virus type 1 mutant is replication defective and demonstrates alterations in both RNA 5'-end- and DNA 3'-end-directed RNase H activities.
Abstract: K103N demonstrated normal RNA 5'-end-directed RNase H cleavage and slowed DNA 3'-end-directed RNase H cleavage compared to wild-type RT.
Abstract: At high concentrations of DLV, P236L replication and K103N replication were both inhibited.
Abstract: At low levels of DLV, growth of wild-type virus was severely inhibited, and K103N replicated two- to threefold more efficiently than P236L.
Abstract: In the absence of DLV, p24 production by wild-type virus occurred more rapidly and to higher levels than with either mutant; P236L consistently demonstrated a two- to threefold decrease in p24 relative to K103N.
Structural determinants of HIV-1 reverse transcriptase stereoselectivity towards (beta)-L-deoxy- and dideoxy-pyrimidine nucleoside triphosphates: molecular basis for the combination of L-dideoxynucleoside analogs with non-nucleoside inhibitors in anti HIV chemotherapy.
Abstract: We have compared the HIV-1 RT mutants containing the single substitutions L100I, K103N, V106A, V179D, Y181I and Y188L, known to confer NNI-resistance in treated patients, to HIV-1 RT wt for their sensitivity towards inhibition by D- and L-deoxy- and dideoxy-nucleoside tiphosphates.
N-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea and N'-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-chloropyridyl)]-thiourea as potent inhibitors of multidrug-resistant human immunodeficiency virus-1.
Abstract: Similarly, both HI-346 and HI-445 were more effective than trovirdine, nevirapine, and delavirdine against the problematic NNI-resistant HIV-1 strain A17-variant with both Y181C and K103N mutations in RT, although their activity was markedly reduced against this strain.
Pyrrolobenzoxazepinone derivatives as non-nucleoside HIV-1 RT inhibitors: further structure-activity relationship studies and identification of more potent broad-spectrum HIV-1 RT inhibitors with antiviral activity.
PMID: 10543890
1999
Journal of medicinal chemistry
Abstract: Compared with the lead 6 and nevirapine, several of the synthesized compounds (PBOs 13a-d and PPOs 13i-k) displayed higher inhibitory activity against wild-type RT and clinically relevant mutant RTs containing the single amino acid substitutions L100I, K103N, V106A, Y181I, and Y188L.
Design of MKC-442 (emivirine) analogues with improved activity against drug-resistant HIV mutants.
PMID: 10579814
1999
Journal of medicinal chemistry
Abstract: Both compounds showed approximately 30-fold greater inhibitory effect than MKC-442 to the Tyr181Cys mutant virus as well as to the clinically important Lys103Asn virus.
Expanded-spectrum nonnucleoside reverse transcriptase inhibitors inhibit clinically relevant mutant variants of human immunodeficiency virus type 1.
PMID: 10582878
1999
Antimicrobial agents and chemotherapy
Abstract: A research program targeted toward the identification of expanded-spectrum nonnucleoside reverse transcriptase inhibitors which possess increased potency toward K103N-containing mutant human immunodeficiency virus (HIV) and which maintain pharmacokinetics consistent with once-a-day dosing has resulted in the identification of the 4-cyclopropylalkynyl-4-trifluoromethyl-3, 4-dihydro-2(1H)quinazolinones DPC 961 and DPC 963 and the 4-cyclopropylalkenyl-4-trifluoromethyl-3, 4-dihydro-2(1H)quinazolinones DPC 082 and DPC 083 for clinical development.
Abstract: DPC 961, DPC 963, DPC 082, and DPC 083 all exhibit low-nanomolar potency toward wild-type virus, K103N and L100I single-mutation variants, and many multiply amino acid-substituted HIV type 1 mutants.
N'-[2-(2-thiophene)ethyl]-N'-[2-(5-bromopyridyl)] thiourea as a potent inhibitor of NNI-resistant and multidrug-resistant human immunodeficiency virus-1.
Abstract: HI-443 inhibited the replication of the NNI-resistant HIV-1 strain A17 variant with Y181C plus K103N mutations in RT with an IC50 value of 3.3 microM, whereas the IC50 values of trovirdine, nevirapine, and delavirdine were all >100 microM.
Efavirenz: resistance and cross-resistance.
PMID: 10622039
1999
International journal of clinical practice. Supplement
Abstract: K103N is found in HIV strains isolated from patients experiencing a viral rebound in plasma HIV-RNA levels who have received an efavirenz-containing regimen.
Abstract: Phenotypic analysis showed that the K103N mutation alone confers an approximate 20-fold increase in the IC50 of efavirenz.
Abstract: With regard to NNRTIs, a single mutation at K103N is the most predominant resistance RT mutation observed with the NNRTIs and confers cross-resistance between efavirenz, nevirapine and delavirdine.
HIV mutation literature information.
PMID: 
2000
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