3LW0

IGF-1RK in complex with ligand MSC1609119A-1

Summary for 3LW0

• Entry DOI: 10.2210/pdb3lw0/pdb
• Descriptor: Insulin-like growth factor 1 receptor, 3-cyano-N-{1-[4-(5-cyano-1H-indol-3-yl)butyl]piperidin-4-yl}-1H-indole-7-carboxamide, GLYCEROL, ... (4 entities in total)
• Functional Keywords: protein kinase, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 142331.72

Authors

Graedler, U.,Heinrich, T.,Boettcher, H.,Blaukat, A.,Shutes, A.,Askew, B. (deposition date: 2010-02-23, release date: 2010-09-29, Last modification date: 2023-11-01)

Primary citation

Heinrich, T.,Gradler, U.,Bottcher, H.,Blaukat, A.,Shutes, A.
Allosteric IGF-1R Inhibitors.
Acs Med.Chem.Lett., 1:199-203, 2010

PubMed 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.

PubMed: 24900194
DOI: 10.1021/ml100044h

Experimental method

X-RAY DIFFRACTION (1.79 Å)