In:
Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 8, No. 12_Supplement ( 2009-12-10), p. A245-A245
Abstract:
The insulin-like growth factor 1 receptor (IGF1R) and its ligands, IGF1 and IGF2 are associated with cell growth and resistance to apoptosis. The ErbB axis, consisting of 4 receptor tyrosine kinases (EGFR, ErbB2, ErbB3, and ErbB4) is a longstanding target of cancer chemotherapy. There is a growing body of literature suggesting that targeting a combination of the IGF and ErbB axes would be more effective than targeting either alone. A screen of Abbott's compound collection revealed a scaffold, the imidazothiazoles, which showed activity against EGFR. A similar scaffold from the literature had previously been reported to have IGF1R activity. Optimization of the imidazothiazoles, and a scaffold hop to imidazopyridines, has provided a series of compounds with amide head groups with kinase inhibitory activity against IGF1R, EGFR, and ErbB2. These compounds also demonstrated inhibition of p-IGF1R and p-EGFR in a human epidermoid carcinoma line (A-431), as well as inhibition of p-ErbB2 in a human gastric cancer cell line (N87). This poster will discuss the synthesis and optimization of the imidazothiazoles and imidazopyridines as multitargeted kinase inhibitors. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A245.
Type of Medium:
Online Resource
ISSN:
1535-7163
,
1538-8514
DOI:
10.1158/1535-7163.TARG-09-A245
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2009
detail.hit.zdb_id:
2062135-8
SSG:
12
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