PDBsum entry 3lw0

Transferase

PDB id: 3lw0

Contents

Protein chains

292 a.a.

Ligands

CCX ×8

GOL ×2

Waters ×1053

References listed in PDB file

Key reference

• Title: Allosteric igf-1r inhibitors.
• Authors: T.Heinrich, U.Grädler, H.Böttcher, A.Blaukat, A.Shutes.
• Ref.: ACS Med Chem Lett, 2010, 1, 199-203. [DOI no: 10.1021/ml100044h]
• PubMed id: 24900194

Abstract

Targeting allosteric protein sites is a promising approach to interfere selectively with cellular signaling cascades. We have discovered a novel class of allosteric insulin-like growth factor-I receptor (IGF-1R) inhibitors. 3-Cyano-1H-indole-7-carboxylic acid {1-[4-(5-cyano-1H-indol-3-yl)butyl]piperidin-4-yl}amide (10) was found with nanomolar biochemical, micromolar, cellular IGF-1R activity and no relevant interference with cellular insulin receptor signaling up to 30 μM. The allosteric binding site was characterized by X-ray crystallographic studies, and the structural information was used to explain the unique mode of action of this new class of inhibitors.