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Basic Characteristics of Mutations
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Mutation Site
|
Y181C |
|
Mutation Site Sentence
|
And also, it displayed potent activities against K103 N (EC50 = 0.077 μM), Y181C (EC50 = 0.11 μM), E138K (EC50 = 0.057 μM), and moderate activity against double mutants RES056 (EC50 = 8.7 μM). |
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Mutation Level
|
Amino acid level |
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Mutation Type
|
Nonsynonymous substitution |
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Gene/Protein/Region
|
RT |
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Standardized Encoding Gene
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gag-pol:155348
|
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Genotype/Subtype
|
HIV-1 |
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Viral Reference
|
-
|
|
Functional Impact and Mechanisms
|
|
Disease
|
HIV Infections
Acquired Immunodeficiency Syndrome
|
|
Immune
|
- |
|
Target Gene
|
-
|
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Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
NNRTIs |
|
Location
|
- |
|
Literature Information
|
|
PMID
|
31767136
|
|
Title
|
Indazolyl-substituted piperidin-4-yl-aminopyrimidines as HIV-1 NNRTIs: Design, synthesis and biological activities
|
|
Author
|
Xiao T,Tang JF,Meng G,Pannecouque C,Zhu YY,Liu GY,Xu ZQ,Wu FS,Gu SX,Chen FE
|
|
Journal
|
European journal of medicinal chemistry
|
|
Journal Info
|
2020 Jan 15;186:111864
|
|
Abstract
|
A series of indazolyl-substituted piperidin-4-yl-aminopyrimidines (IPAPYs) were designed from two potent HIV-1 NNRTIs piperidin-4-yl-aminopyrimidine 3c and diaryl ether 4 as the lead compounds by molecular hybridization strategy. The target molecules 5a-q were synthesized and evaluated for their anti-HIV activities and cytotoxicities in MT-4 cells. 5a-q displayed moderate to excellent activities against wild-type (WT) HIV-1 with EC50 values ranging from 1.5 to 0.0064 muM. Among them, 5q was regarded as the most excellent compound against WT HIV-1 (EC50 = 6.4 nM, SI = 2500). And also, it displayed potent activities against K103 N (EC50 = 0.077 muM), Y181C (EC50 = 0.11 muM), E138K (EC50 = 0.057 muM), and moderate activity against double mutants RES056 (EC50 = 8.7 muM). Moreover, the structure-activity relationships (SARs) were summarized, and the molecular docking was performed to investigate the binding mode of IPAPYs and HIV-1 reverse transcriptase.
|
|
Sequence Data
|
-
|
|
|