Discovery of the first non-ATP competitive IGF-1R kinase inhibitors: advantages in comparison with competitive inhibitors

Dominique Lesuisse; Jacques Mauger; Conception Nemecek; Sébastien Maignan; Janine Boiziau; Greg Harlow; Augustin Hittinger; Swen Ruf; Hartmut Strobel; Anil Nair; Kurt Ritter; Jean-Luc Malleron; Anne Dagallier; Youssef El-Ahmad; Jean-Pierre Guilloteau; Houlfa Guizani; Hervé Bouchard; Corinne Venot

doi:10.1016/j.bmcl.2011.03.003

Discovery of the first non-ATP competitive IGF-1R kinase inhibitors: advantages in comparison with competitive inhibitors

Bioorg Med Chem Lett. 2011 Apr 15;21(8):2224-8. doi: 10.1016/j.bmcl.2011.03.003. Epub 2011 Mar 4.

Authors

Dominique Lesuisse¹, Jacques Mauger, Conception Nemecek, Sébastien Maignan, Janine Boiziau, Greg Harlow, Augustin Hittinger, Swen Ruf, Hartmut Strobel, Anil Nair, Kurt Ritter, Jean-Luc Malleron, Anne Dagallier, Youssef El-Ahmad, Jean-Pierre Guilloteau, Houlfa Guizani, Hervé Bouchard, Corinne Venot

Affiliation

¹ Medicinal Chemistry, Sanofi-aventis, 13 Quai Jules Guesde, 94300 Vitry-sur-Seine, France. dominique.lesuisse@sanofi-aventis.com

PMID: 21441024
DOI: 10.1016/j.bmcl.2011.03.003

Abstract

A new series of IGF-1R inhibitors related to hydantoins were identified from a lead originating from HTS. Their noncompetitive property as well as their slow binding characteristics provided a series of compounds with unique selectivity and excellent cellular activities.

MeSH terms

Adenosine Triphosphate / chemistry
Animals
Binding Sites
Binding, Competitive
Computer Simulation
Drug Evaluation, Preclinical
Mice
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacokinetics
Receptor, IGF Type 1 / antagonists & inhibitors*
Receptor, IGF Type 1 / metabolism

Substances

Protein Kinase Inhibitors
Adenosine Triphosphate
Receptor, IGF Type 1