AZD4320, A Dual Inhibitor of Bcl-2 and Bcl-x

Animals Antineoplastic Agents / pharmacology Apoptosis Benzamides / pharmacology Cell Proliferation Female Hematologic Neoplasms / drug therapy Humans Mice Mice, Inbred NOD Mice, SCID Piperidines / pharmacology Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors Sulfones / pharmacology Thrombocytopenia / drug therapy Tumor Cells, Cultured Xenograft Model Antitumor Assays bcl-X Protein / antagonists & inhibitors

Journal

Clinical cancer research : an official journal of the American Association for Cancer Research

ISSN: 1557-3265

Titre abrégé: Clin Cancer Res

Pays: United States

ID NLM: 9502500

Informations de publication

Date de publication:
15 12 2020

Historique:

received: 19 03 2020

revised: 24 07 2020

accepted: 22 09 2020

pubmed: 30 9 2020

medline: 15 12 2021

entrez: 29 9 2020

Statut: ppublish

Résumé

Targeting Bcl-2 family members upregulated in multiple cancers has emerged as an important area of cancer therapeutics. While venetoclax, a Bcl-2-selective inhibitor, has had success in the clinic, another family member, Bcl-x We used structure-based chemistry to design a small-molecule inhibitor of Bcl-2 and Bcl-x We discovered AZD4320, which has nanomolar affinity for Bcl-2 and Bcl-x AZD4320 is a potent molecule with manageable thrombocytopenia risk to explore the utility of a dual Bcl-2/Bcl-x

Identifiants

DOI: 10.1158/1078-0432.CCR-20-0863 PMID: 32988967

pubmed: 32988967

pii: 1078-0432.CCR-20-0863

doi: 10.1158/1078-0432.CCR-20-0863

doi:

Substances chimiques

AZD4320 0

Antineoplastic Agents 0

BCL2 protein, human 0

BCL2L1 protein, human 0

Benzamides 0

Piperidines 0

Proto-Oncogene Proteins c-bcl-2 0

Sulfones 0

bcl-X Protein 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

6535-6549

Subventions

Organisme : Wellcome Trust

ID : 206194

Pays : United Kingdom

Organisme : Wellcome Trust

ID : 206194

Pays : United Kingdom

Informations de copyright

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