Development of novel inhibitors targeting HIF-1α towards anticancer drug discovery.

Autor: Yewalkar N; Department of Medicinal Chemistry, Piramal Life Sciences, 1-Nirlon Complex, Off Western Express Highway, Goregaon (E), Mumbai 400 063, India., Deore V, Padgaonkar A, Manohar S, Sahu B, Kumar P, Jalota-Badhwar A, Joshi KS, Sharma S, Kumar S
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2010 Nov 15; Vol. 20 (22), pp. 6426-9. Date of Electronic Publication: 2010 Sep 18.
DOI: 10.1016/j.bmcl.2010.09.083
Abstrakt: Hypoxia-inducible factor-1α (HIF-1α) is a critical regulatory protein of cellular response to hypoxia, and regulates the transcription of many genes involved in key aspects of cancer biology, including immortalization, maintenance of stem cell pools, cellular dedifferentiation, vascularization, and invasion/metastasis. HIF-1α has been implicated in the regulation of genes involved in angiogenesis, for example, VEGF and is associated with tumor progression. In the last decade, over expression of HIF-1α has been demonstrated in many common human cancers and emerging as a validated target for anticancer drug discovery. Here we report the discovery of newly designed and synthesized pyridylpyrimidine based potent and selective inhibitors of HIF-1α. P2630 has been found as potent antiproliferative, antiangiogenic and orally efficacious compound in PC-3 xenograft mice model.
(Copyright © 2010 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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