1446322-63-9Relevant academic research and scientific papers
A cyclic peptide inhibitor of HIF-1 heterodimerization that inhibits hypoxia signaling in cancer cells
Miranda, Elena,Nordgren, Ida K.,Male, Abigail L.,Lawrence, Charlotte E.,Hoakwie, Franciane,Cuda, Francesco,Court, William,Fox, Keith R.,Townsend, Paul A.,Packham, Graham K.,Eccles, Suzanne A.,Tavassoli, Ali
supporting information, p. 10418 - 10425 (2013/08/23)
Hypoxia inducible factor-1 (HIF-1) is a heterodimeric transcription factor that acts as the master regulator of cellular response to reduced oxygen levels, thus playing a key role in the adaptation, survival, and progression of tumors. Here we report cyclo-CLLFVY, identified from a library of 3.2 million cyclic hexapeptides using a genetically encoded high-throughput screening platform, as an inhibitor of the HIF-1α/HIF-1β protein-protein interaction in vitro and in cells. The identified compound inhibits HIF-1 dimerization and transcription activity by binding to the PAS-B domain of HIF-1α, reducing HIF-1-mediated hypoxia response signaling in a variety of cell lines, without affecting the function of the closely related HIF-2 isoform. The reported cyclic peptide demonstrates the utility of our high-throughput screening platform for the identification of protein-protein interaction inhibitors, and forms the starting point for the development of HIF-1 targeted cancer therapeutics.
