Molecular glues and induced proximity: An evolution of tools and discovery

Stephanie Anne Robinson; Jennifer Anne Co; Steven Mark Banik

doi:10.1016/j.chembiol.2024.04.001

Molecular glues and induced proximity: An evolution of tools and discovery

Cell Chem Biol. 2024 Apr 22:S2451-9456(24)00129-6. doi: 10.1016/j.chembiol.2024.04.001. Online ahead of print.

Authors

Stephanie Anne Robinson¹, Jennifer Anne Co¹, Steven Mark Banik²

Affiliations

¹ Department of Chemistry, Stanford University, Stanford, CA, USA.
² Department of Chemistry, Stanford University, Stanford, CA, USA; Sarafan ChEM-H, Stanford University, Stanford, CA, USA. Electronic address: sbanik@stanford.edu.

PMID: 38688281
DOI: 10.1016/j.chembiol.2024.04.001

Abstract

Small molecule molecular glues can nucleate protein complexes and rewire interactomes. Molecular glues are widely used as probes for understanding functional proximity at a systems level, and the potential to instigate event-driven pharmacology has motivated their application as therapeutics. Despite advantages such as cell permeability and the potential for low off-target activity, glues are still rare when compared to canonical inhibitors in therapeutic development. Their often simple structure and specific ability to reshape protein-protein interactions pose several challenges for widespread, designer applications. Molecular glue discovery and design campaigns can find inspiration from the fields of synthetic biology and biophysics to mine chemical libraries for glue-like molecules.

Keywords: chemically induced proximity; molecular glues; phenotypic and molecular screens; synthetic biology.

Publication types

Review