A two-faced selectivity solution to target SMARCA2 for cancer therapy

John D Harling; Christopher P Tinworth

doi:10.1038/s41467-023-36238-0

A two-faced selectivity solution to target SMARCA2 for cancer therapy

Nat Commun. 2023 Jan 31;14(1):515. doi: 10.1038/s41467-023-36238-0.

Authors

John D Harling¹, Christopher P Tinworth²

Affiliations

¹ Dept. of Medicinal Chemistry, GSK, Gunnels Wood Road, Stevenage, SG1 2NY, UK. [email protected].
² Dept. of Medicinal Chemistry, GSK, Gunnels Wood Road, Stevenage, SG1 2NY, UK.

Abstract

Two new studies exploring PROTAC-mediated degradation of SMARCA2 for cancer therapy solve an apparently intractable selectivity challenge with SMARCA4 by utilising the requirement for a productive ternary complex between the protein, PROTAC and ligase complex.

MeSH terms

Humans
Neoplasms* / drug therapy
Neoplasms* / genetics
Transcription Factors / genetics

Substances

SMARCA2 protein, human
Transcription Factors