4.7 Article

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

相关参考文献

注意:仅列出部分参考文献,下载原文获取全部文献信息。
Article Microbiology

GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile

Ira Dicker et al.

Summary: HIV-1 maturation inhibitor GSK3640254 (GSK'254) demonstrates strong antiviral activity against a wide range of HIV-1 strains with Gag polymorphisms, but potential resistance can occur. This study provides insights into the antiviral and resistance profiles of GSK'254, highlighting its efficacy and the mechanism of resistance.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2022)

Article Immunology

Phase IIa Proof-of-Concept Evaluation of the Antiviral Efficacy, Safety, Tolerability, and Pharmacokinetics of the Next-Generation Maturation Inhibitor GSK3640254

Christoph D. Spinner et al.

Summary: This study evaluated the use of GSK'254 in HIV-1-positive patients. The results showed that GSK'254 has antiviral effects and does not cause significant safety or tolerability concerns. These results provide the basis for dose selection in future studies.

CLINICAL INFECTIOUS DISEASES (2022)

Review Pharmacology & Pharmacy

Update and latest advances in antiretroviral therapy

Luis Menendez-Arias et al.

Summary: Since the first cases of AIDS appeared in 1981, HIV-1 infection has become a global pandemic, but research has led to the approval of over 30 antiretroviral drugs and combination therapies turning HIV-1 infection into a chronic but manageable disease. However, drug toxicity and acquired and transmitted drug resistance remain major threats to therapy success.

TRENDS IN PHARMACOLOGICAL SCIENCES (2022)

Article Pharmacology & Pharmacy

Relative Bioavailability and Food Effect of GSK3640254 Tablet and Capsule Formulations in Healthy Participants

Mark Johnson et al.

Summary: This study assessed the relative bioavailability of GSK3640254 tablet and capsule formulations in healthy participants and investigated the effect of food on the pharmacokinetics of the tablet formulation. The results showed that there was no meaningful difference in plasma exposures between the tablet and capsule formulations when administered with a moderate-fat meal. Under high- and moderate-fat conditions, the plasma exposures of the tablet formulation increased by approximately 3- to 4-fold compared with fasted conditions.

CLINICAL PHARMACOLOGY IN DRUG DEVELOPMENT (2022)

Article Chemistry, Medicinal

Design and exploration of C-3 benzoic acid bioisosteres and alkyl replacements in the context of GSK3532795 (BMS-955176) that exhibit broad spectrum HIV-1 maturation inhibition

Jacob J. Swidorski et al.

Summary: GSK3532795, a second-generation HIV-1 maturation inhibitor, demonstrated broad spectrum antiviral activity but faced challenges in clinical trials. Evaluation of alternatives to the C-3 phenyl substituent in this class of drugs showed promising results in addressing issues encountered with GSK3532795.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2021)

Article Microbiology

Inositol phosphates promote HIV-1 assembly and maturation to facilitate viral spread in human CD4+ T cells

Gregory A. Sowd et al.

Summary: Our study demonstrates that inositol phosphates, IP5 and IP6, play crucial roles in HIV-1 assembly and maturation. Depletion of IP5 and IP6 in T cells resulted in impaired viral particle assembly and reduced infectivity of produced virions. These findings suggest that targeting HIV-1 inositol phosphate binding pockets may inhibit distinct aspects of HIV-1 replication.

PLOS PATHOGENS (2021)

Article Chemistry, Medicinal

Bioisosteres of the Phenyl Ring: Recent Strategic Applications in Lead Optimization and Drug Design

Murugaiah A. M. Subbaiah et al.

Summary: The benzene moiety is commonly found in drugs, but its indiscriminate use can lead to poor physicochemical properties. Bioisosteric replacements for benzene rings can improve potency, solubility, and metabolic stability while reducing lipophilicity and other negative effects.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Chemistry, Multidisciplinary

Preservation of HIV-1 Gag Helical Bundle Symmetry by Bevirimat Is Central to Maturation Inhibition

Alexander J. Pak et al.

Summary: This study utilized molecular dynamics simulations and free energy calculations to quantitatively investigate molecular structure-activity relationships of the maturation inhibitor Bevirimat (BVM) in HIV-1 assembly. The efficacy of BVM was found to be directly correlated with preservation of 6-fold symmetry in the 6HB, and two primary escape mechanisms were identified leading to loss of symmetry. Specific interactions for improved inhibitor activity were highlighted, supporting the use of MD simulations for future inhibitor design.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2021)

Article Pharmacology & Pharmacy

Phase I evaluation of pharmacokinetics and tolerability of the HIV-1 maturation inhibitor GSK3640254 and dolutegravir in healthy adults

Teodora Pene Dumitrescu et al.

Summary: The study demonstrated that the coadministration of GSK3640254 with dolutegravir showed good pharmacokinetics and tolerability, without significant drug interactions, and no clinically significant adverse trends were observed.

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY (2021)

Review Virology

The HIV-1 capsid and reverse transcription

Christopher Aiken et al.

Summary: Recent studies have shown that the viral capsid plays a key role in HIV-1 reverse transcription, with the small molecule IP6 enhancing this process significantly. Reverse transcription leads to marked changes in the biophysical properties of the capsid, ultimately causing its breakage and disassembly.

RETROVIROLOGY (2021)

Article Multidisciplinary Sciences

A stable immature lattice packages IP6 for HIV capsid maturation

Donna L. Mallery et al.

Summary: HIV maintains immature lattice stability to ensure IP6 packaging while allowing maturation. Mutant viruses with reduced IP6 recruitment show increased infectivity upon treatment with MIs or second-site compensatory mutations.

SCIENCE ADVANCES (2021)

Article Microbiology

A Phase I Evaluation of the Pharmacokinetics and Tolerability of the HIV-1 Maturation Inhibitor GSK3640254 and Tenofovir Alafenamide/Emtricitabine in Healthy Participants

Teodora Pene Dumitrescu et al.

Summary: The study found that coadministration of GSK3640254 with TAF/FTC resulted in slightly lower TAF plasma concentrations and maximum observed concentrations compared to when TAF/FTC was administered alone, while the pharmacokinetics of TFV and FTC were similar. GSK3640254 did not significantly affect the steady-state pharmacokinetics of TAF, TFV, or FTC in healthy participants under fed conditions.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2021)

Article Biology

CryoET structures of immature HIV Gag reveal six-helix bundle

Luiza Mendonca et al.

Summary: In this study, the structures of both in vitro assemblies of the HIV structural precursor protein Gag and Gag viral-like particles (VLPs) were determined to resolutions of 4.2 angstrom and 4.5 angstrom, providing insights for the future development of small molecule inhibitors for HIV-1 infection. Additionally, a single amino acid mutation (T8I) in SP1 was shown to stabilize the six-helix bundle, potentially aiding in the design of inhibitors to block HIV maturation and infection.

COMMUNICATIONS BIOLOGY (2021)

Review Chemistry, Organic

Diethylaminosulfur Trifluoride (DAST) Mediated Transformations Leading to Valuable Building Blocks and Bioactive Compounds

Marcin Kazmierczak et al.

Summary: This minireview focuses on nucleophilic fluorination reactions mediated by diethylaminosulfur trifluoride (DAST) and their applications in synthesizing valuable building blocks and bioactive compounds. Various transformations, including beta-amino alcohols, heterocyclic frameworks synthesis, and rearrangement reactions, are discussed in detail based on literature published since 2010.

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY (2021)

Review Virology

A Structural Perspective of the Role of IP6 in Immature and Mature Retroviral Assembly

Martin Obr et al.

Summary: IP6, a small cellular molecule, facilitates the assembly of HIV-1 and other retroviruses into virus-like particles in vitro, enhancing core stability during reverse transcription process.

VIRUSES-BASEL (2021)

Review Pharmacology & Pharmacy

Uridine diphosphate glucuronosyltransferase 1A1

Glyn Steventon

XENOBIOTICA (2020)

Review Pharmacology & Pharmacy

Combination therapies currently under investigation in phase I and phase II clinical trials for HIV-1

Hanh Thi Pham et al.

EXPERT OPINION ON INVESTIGATIONAL DRUGS (2020)

Article Multidisciplinary Sciences

Effects of an HIV-1 maturation inhibitor on the structure and dynamics of CA-SP1 junction helices in virus-like particles

Sebanti Gupta et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

Review Chemistry, Multidisciplinary

Recent Advances in the Protection of Amine Functionality: A Review

Jyoti Omprakash Rathi et al.

CHEMISTRYSELECT (2020)

Review Biochemistry & Molecular Biology

Impact of Cross-Coupling Reactions in Drug Discovery and Development

Melissa J. Buskes et al.

MOLECULES (2020)

Review Virology

HIV-1 Maturation: Lessons Learned from Inhibitors

Alex B. Kleinpeter et al.

VIRUSES-BASEL (2020)

Article Pharmacology & Pharmacy

Phase I evaluation of the safety, tolerability, and pharmacokinetics of GSK3640254, a next-generation HIV-1 maturation inhibitor

Samit R. Joshi et al.

PHARMACOLOGY RESEARCH & PERSPECTIVES (2020)

Review Pharmacology & Pharmacy

Assessment of Pharmacokinetic Drug-Drug Interactions in Humans: In Vivo Probe Substrates for Drug Metabolism and Drug Transport Revisited

Uwe Fuhr et al.

ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 59 (2019)

Article Chemistry, Medicinal

Second Generation Inhibitors of HIV-1 Maturation

Alicia Regueiro-Ren et al.

ACS MEDICINAL CHEMISTRY LETTERS (2019)

Review Virology

Multiple Roles of HIV-1 Capsid during the Virus Replication Cycle

Mariia Novikova et al.

VIROLOGICA SINICA (2019)

Review Pharmacology & Pharmacy

Next generation fixed dose combination pharmacotherapies for treating HIV

Margaret R. Caplan et al.

EXPERT OPINION ON PHARMACOTHERAPY (2018)

Article Chemistry, Medicinal

Fluorine and Fluorinated Motifs in the Design and Application of Bioisosteres for Drug Design

Nicholas A. Meanwell

JOURNAL OF MEDICINAL CHEMISTRY (2018)

Article Multidisciplinary Sciences

Inositol phosphates are assembly co-factors for HIV-1

Robert A. Dick et al.

NATURE (2018)

Article Virology

The Human Immunodeficiency Virus Capsid Is More Than Just a Genome Package

Leo C. James et al.

ANNUAL REVIEW OF VIROLOGY, VOL 5 (2018)

Article Multidisciplinary Sciences

MicroED structures of HIV-1 Gag CTD-SP1 reveal binding interactions with the maturation inhibitor bevirimat

Michael D. Purdy et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2018)

Review Virology

IP6 Regulation of HIV Capsid Assembly, Stability, and Uncoating

Robert A. Dick et al.

VIRUSES-BASEL (2018)

Review Biochemistry & Molecular Biology

Drug-Target Kinetics in Drug Discovery

Peter J. Tonge

ACS CHEMICAL NEUROSCIENCE (2018)

Article Biochemistry & Molecular Biology

HIV Capsid Assembly, Mechanism, and Structure

Bo Chen

BIOCHEMISTRY (2016)

Article Biochemistry & Molecular Biology

C-3 benzoic acid derivatives of C-3 deoxybetulinic acid and deoxybetulin as HIV-1 maturation inhibitors

Zheng Liu et al.

BIOORGANIC & MEDICINAL CHEMISTRY (2016)

Article Multidisciplinary Sciences

An atomic model of HIV-1 capsid-SP1 reveals structures regulating assembly and maturation

Florian K. M. Schur et al.

SCIENCE (2016)

Article Chemistry, Medicinal

Discovery of BMS-955176, a Second Generation HIV-1 Maturation Inhibitor with Broad Spectrum Antiviral Activity

Alicia Regueiro-Ren et al.

ACS MEDICINAL CHEMISTRY LETTERS (2016)

Article Biology

Crystal structure of an HIV assembly and maturation switch

Jonathan M. Wagner et al.

Article Chemistry, Medicinal

Applications of Fluorine in Medicinal Chemistry

Eric P. Gillis et al.

JOURNAL OF MEDICINAL CHEMISTRY (2015)

Review Microbiology

HIV-1 assembly, release and maturation

Eric O. Freed

NATURE REVIEWS MICROBIOLOGY (2015)

Review Microbiology

HIV-1 capsid: the multifaceted key player in HIV-1 infection

Edward M. Campbell et al.

NATURE REVIEWS MICROBIOLOGY (2015)

Article Multidisciplinary Sciences

Structure of the immature HIV-1 capsid in intact virus particles at 8.8 Å resolution

Florian K. M. Schur et al.

NATURE (2015)

Article Multidisciplinary Sciences

Structure of the immature retroviral capsid at 8 Å resolution by cryo-electron microscopy

Tanmay A. M. Bharat et al.

NATURE (2012)

Editorial Material Immunology

Can the further clinical development of bevirimat be justified?

Mark A. Wainberg et al.

Article Microbiology

Phenotypic Susceptibility to Bevirimat in Isolates from HIV-1-Infected Patients without Prior Exposure to Bevirimat

Nicolas A. Margot et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2010)

Article Biochemical Research Methods

Predicting Bevirimat resistance of HIV-1 from genotype

Dominik Heider et al.

BMC BIOINFORMATICS (2010)

Article Biochemistry & Molecular Biology

HIV-1 Gag Processing Intermediates Trans-dominantly Interfere with HIV-1 Infectivity

Barbara Mueller et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2009)

Article Pharmacology & Pharmacy

An Oral Human Drug Absorption Study to Assess the Impact of Site of Delivery on the Bioavailability of Bevirimat

Alyson Connor et al.

JOURNAL OF CLINICAL PHARMACOLOGY (2009)

Article Multidisciplinary Sciences

Structure and assembly of immature HIV

J. A. G. Briggs et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2009)

Article Biochemistry & Molecular Biology

Interactions between HIV-1 Gag molecules in solution: An inositol phosphate-mediated switch

Siddhartha A. K. Datta et al.

JOURNAL OF MOLECULAR BIOLOGY (2007)

Review Chemistry, Medicinal

Acyl glucuronides: Biological activity, chemical reactivity, and chemical synthesis

Andrew V. Stachulski et al.

JOURNAL OF MEDICINAL CHEMISTRY (2006)

Article Biochemistry & Molecular Biology

Bicyclic[4.1.0]heptanes as phenyl replacements for melanin concentrating hormone receptor antagonists

R Xu et al.

BIOORGANIC & MEDICINAL CHEMISTRY (2006)

Review Chemistry, Multidisciplinary

Proteases universally recognize beta strands in their active sites

JDA Tyndall et al.

CHEMICAL REVIEWS (2005)

Article Multidisciplinary Sciences

PA-457: A potent HIV inhibitor that disrupts core condensation by targeting a late step in Gag processing

F Li et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2003)

Article Multidisciplinary Sciences

Modulation of HIV-like particle assembly in vitro by inositol phosphates

S Campbell et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2001)