2zm3

File:2zm3.png

Complex Structure of Insulin-like Growth Factor Receptor and Isoquinolinedione Inhibitor

OverviewOverview

Insulin-like growth factor receptor (IGF-1R) is a growth factor receptor tyrosine kinase that acts as a critical mediator of cell proliferation and survival. This receptor is over-expressed or activated in tumor cells and is emerging as a novel target in cancer therapy. Efforts in our "Hit to Lead" group have generated a novel series of submicromolar IGF-1R inhibitors based on a isoquinolinedione template originating from a Lance enzyme HTS screen. Chemical triage and parallel synthesis incorporating focused library arrays were instrumental in moving these investigations through the Wyeth exploratory medicinal chemistry process. The strategies, synthesis, and SAR behind this interesting kinase scaffold will be described.

DiseaseDisease

Known disease associated with this structure: Intrauterine and postnatal growth retardation OMIM:[147370]

About this StructureAbout this Structure

2ZM3 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Lead identification to generate isoquinolinedione inhibitors of insulin-like growth factor receptor (IGF-1R) for potential use in cancer treatment., Mayer SC, Banker AL, Boschelli F, Di L, Johnson M, Kenny CH, Krishnamurthy G, Kutterer K, Moy F, Petusky S, Ravi M, Tkach D, Tsou HR, Xu W, Bioorg Med Chem Lett. 2008 Jun 15;18(12):3641-5. Epub 2008 Apr 25. PMID:18501599

Page seeded by OCA on Wed Jun 25 15:11:11 2008