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Basic Characteristics of Mutations
|
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Mutation Site
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E138K |
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Mutation Site Sentence
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They displayed up to single-digit nanomolar activity against wild-type (WT) and rilpivirine-associated resistant mutant E138K viruses, as well as potent inhibitory ability toward the RT enzyme. |
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Mutation Level
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Amino acid level |
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Mutation Type
|
Nonsynonymous substitution |
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Gene/Protein/Region
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RT |
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Standardized Encoding Gene
|
gag-pol:155348
|
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Genotype/Subtype
|
HIV-1 |
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Viral Reference
|
-
|
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Functional Impact and Mechanisms
|
|
Disease
|
Acquired Immunodeficiency Syndrome
|
|
Immune
|
- |
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Target Gene
|
-
|
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Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
rilpivirine;NNRTIs;novel naphthyl-carboxamide-diarylpyrimidine derivatives a1 |
|
Location
|
- |
|
Literature Information
|
|
PMID
|
33895602
|
|
Title
|
Chemical space exploration of novel naphthyl-carboxamide-diarylpyrimidine derivatives with potent anti-HIV-1 activity
|
|
Author
|
Sang Y,Pannecouque C,De Clercq E,Zhuang C,Chen F
|
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Journal
|
Bioorganic chemistry
|
|
Journal Info
|
2021 Jun;111:104905
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Abstract
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Fifteen naphthyl-carboxamide-DAPYs were generated to explore chemical space in reverse transcriptase (RT) binding site via lead optimization strategy. They displayed up to single-digit nanomolar activity against wild-type (WT) and rilpivirine-associated resistant mutant E138K viruses, as well as potent inhibitory ability toward the RT enzyme. Compound a1 showed exceptionally inhibitory effects with an EC(50) value of 3.7 nM against HIV-1 wt strain, and an EC(50) of 11 nM targeting mutant E138K. The structure-activity relationships (SARs) of the newly obtained DAPYs were also investigated. Molecular docking analysis elucidated the biological activity and offered a structural insight for follow-up research.
|
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Sequence Data
|
-
|