Lead identification to generate isoquinolinedione inhibitors of insulin-like growth factor receptor (IGF-1R) for potential use in cancer treatment.

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Citation

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

Lead identification to generate isoquinolinedione inhibitors of insulin-like growth factor receptor (IGF-1R) for potential use in cancer treatment.

Bioorg Med Chem Lett. 2008 Jun 15;18(12):3641-5. doi: 10.1016/j.bmcl.2008.04.044. Epub 2008 Apr 25.

PubMed ID
18501599 [ View in PubMed
]
Abstract

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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Insulin-like growth factor 1 receptorP08069Details