Structure-based discovery of novel piperidine-biphenyl-DAPY derivatives as non-nucleoside reverse transcriptase inhibitors featuring improved potency, safety, and selectivity: From piperazine-biphenyl-DAPYs to piperidine-biphenyl-DAPYs

European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 276, С. 116668 - 116668

Опубликована: Июль 10, 2024

Язык: Английский

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The Discovery of GSK3640254, a Next-Generation Inhibitor of HIV-1 Maturation

Journal of Medicinal Chemistry, Год журнала: 2022, Номер 65(18), С. 11927 - 11948

Опубликована: Авг. 31, 2022

GSK3640254 is an HIV-1 maturation inhibitor (MI) that exhibits significantly improved antiviral activity toward a range of clinically relevant polymorphic variants with reduced sensitivity the second-generation MI GSK3532795 (BMS-955176). The key structural difference between and its predecessor replacement para-substituted benzoic acid moiety attached at C-3 position triterpenoid core cyclohex-3-ene-1-carboxylic substituted CH2F carbon atom α- to pharmacophoric carboxylic acid. This element provided new vector which explore structure-activity relationships (SARs) led compounds coverage while preserving pharmacokinetic (PK) properties. approach design GSK3640254, development synthetic route preclinical profile are discussed. currently in phase IIb clinical trials after demonstrating dose-related reduction viral load over 7-10 days dosing HIV-1-infected subjects.

Язык: Английский

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The HIV-1 gag p6: a promising target for therapeutic intervention

Retrovirology, Год журнала: 2024, Номер 21(1)

Опубликована: Янв. 23, 2024

Abstract The p6 domain of the Gag precursors (Gag p6) in human immunodeficiency virus type 1 (HIV-1) plays multifunctional roles viral life cycle. It utilizes endosomal sorting complex required for transport (ESCRT) system to facilitate budding and release from plasma membrane through interactions with ESCRT-I component tumor susceptibility gene 101 (TSG101) ALG-2 interacting protein X (ALIX). Moreover, contributes replication by a range posttranslational modifications such as SUMOylation, ubiquitination phosphorylation. Additionally, also mediates incorporation accessory Vpr into virions, thereby promoting Vpr-induced replication. However, less attention is focused on therapeutic intervention. This review focuses structures diverse functions replication, host cells, pathogenesis. several challenges were discussed studying structure its partners. Consequently, it concludes that represents an attractive target development antiretroviral drugs, efforts develop p6-targeted antiretrovirals are expected undergo significant growth forthcoming years.

Язык: Английский

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Twice-yearly Lenacapavir demonstrated exceptional efficacy for HIV prevention

The Innovation, Год журнала: 2024, Номер 5(5), С. 100683 - 100683

Опубликована: Авг. 8, 2024

Язык: Английский

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p62 Binding to Protein Kinase C Regulates HIV-1 gp120 V3 Loop Induced Microglial Inflammation

Inflammation, Год журнала: 2024, Номер unknown

Опубликована: Дек. 28, 2024

Язык: Английский

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