POSTPONED - New Date TBD: Biology Department Seminar

Hypoxia-inducible factor-1alpha (HIF-1alpha) 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-1alpha has been implicated in the regulation of genes involved in angiogenesis e.g. VEGF and is associated with tumor progression. In last decade, the over expression of HIF-1alpha has been demonstrated in many common human cancers and has emerged as a validated target for anticancer drug discovery. In the present talk design and synthesis of pyridyl-pyrimidine/ pyridyl-oxadiazole based HIF-1alpha inhibitors will be discussed1. There is growing evidence that selective / single target inhibitors2 may not serve the purpose for treating cancer and hence the quest for the discovery of multiple target inhibitors3,4 is emerging as a choice, which will be covered briefly in the present talk.
References: (1) Sanjay Kumar et al., Pyridyl derivatives, their preparation and use, WO 2009 / 019656 A1. (2) Vijaykumar Deore et al., An efficient synthesis of key intermediate towards Liphagal synthesis. Synth. Comm. 2009 (In-press). (3) Manoj V. Lohar et al., Design and Synthesis of Novel Furoquinoline Based Inhibitors of Multiple Targets in the PI3K/Akt-mTOR Pathway. Bioorg. Med. Chem. Lett. 2008, 18, 3603-3609. (4) Mandar R. Bonde et al., Efficacious in a Murine Model of Colitis, Am. J. Physiology (Gastrointestinal & Liver Physiology), 2008, 295, G1237-G1245.