Discover Community Create You

Loading publication...

Noodle always counts identifier-free feature events for service operation. With your permission, Google Analytics can also estimate audience and engagement. Search text, publication identifiers, cookies, IP addresses and browser fingerprints are never included in Noodle's first-party event counters.

Privacy details

Article

Structural insights into chemoresistance mutants of BCL-2 and their targeting by stapled BAD BH3 helices.

Nature communications - 29 Sept 2025

DeAngelo Thomas M, Adhikary Utsarga, Korshavn Kyle J, Seo Hyuk-Soo, Brotzen-Smith Clara R, Camara Christina M, Dhe-Paganon Sirano, Bird Gregory H, Wales Thomas E, Walensky Loren D

Abstract excerpt

BCL-2 is a central regulator of apoptosis and inhibits cell death by sequestering pro-apoptotic BH3 alpha-helices within a hydrophobic surface groove. While venetoclax, a BH3-mimetic drug, has transformed the treatment of BCL-2-driven malignancies, its efficacy is increasingly limited by acquired resistance mutations that disrupt small-molecule binding yet preserve anti-apoptotic function-reflecting a remarkable...

Read the complete abstract on PubMed

Topics

Share this publication in a Topic to start or enrich a Post.

Share to Antineoplastic Agents
Share to bcl-Associated Death Protein

Methodology Data sources Editorial policy Privacy Delete account & data About Contact Helena Bioinformatics

Share to Bridged Bicyclo Compounds, Heterocyclic

Share to Crystallography, X-Ray

Share to Drug Resistance, Neoplasm

Share to Protein Conformation, alpha-Helical

Share to Proto-Oncogene Proteins c-bcl-2

Share to Sulfonamides

Source

Open in PubMed Open full text

Identifiers

PMID: 41022713
DOI: 10.1038/s41467-025-63657-y
PMCID: PMC12480952

Genes

BAD
HDX

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 8 Sept 2026.

Related research

Semantic proximity does not establish scientific evidence.

Research trail→

Click a neighbor to travelStep 1 · 12 closest

Structural insights into chemoresistance mutants of BCL-2 and their targeting by stapled BAD BH3 helices.PMID 41022713Read ↗

Conformational changes in Bcl-2 pro-survival proteins determine their capacity to bind ligands.Semantic proximity Read ↗

Targeting BCL2 With BH3 Mimetics: Basic Science and Clinical Application of Venetoclax in Chronic Lymphocytic Leukemia and Related B Cell MalignanciesSemantic proximity Read ↗

Cyclic peptides discriminate BCL-2 and its clinical mutants from BCL-XL by engaging a single-residue discrepancySemantic proximity Read ↗

Iterative optimization yields Mcl-1-targeting stapled peptides with selective cytotoxicity to Mcl-1-dependent cancer cells.Semantic proximity Read ↗

BH3 Mimetics for the Treatment of B-Cell Malignancies—Insights and Lessons from the ClinicSemantic proximity Read ↗

Discovery, development and application of drugs targeting BCL-2 pro-survival proteins in cancerSemantic proximity Read ↗

Epistatic mutations in PUMA BH3 drive an alternate binding mode to potently and selectively inhibit anti-apoptotic Bfl-1.Semantic proximity Read ↗

Structural Details of BH3 Motifs and BH3-Mediated Interactions: an Updated PerspectiveSemantic proximity Read ↗

Inhibition of Pro-apoptotic BAX by a noncanonical interaction mechanism.Semantic proximity Read ↗

The BCL-2 arbiters of apoptosis and their growing role as cancer targetsSemantic proximity Read ↗

Structures of BCL-2 in complex with venetoclax reveal the molecular basis of resistance mutationsSemantic proximity Read ↗

Targeting anti‐apoptotic BCL 2 family proteins in haematological malignancies – from pathogenesis to treatmentSemantic proximity Read ↗

⌁Select a neighboring publication to make it the new centre.