Alpha subunit of the hypoxia-inducible factor 1 (HIF-1α) is an important transcriptional regulator of hypoxia-inducible genes responsible for tumor proliferation and metastasis, and therefore HIF-1α is a valuable therapeutic target. In turn, the interaction between C-terminal activation domain (C-TAD) of HIF-1α and the cysteine-histidine rich domain (CH1) of its coactivator p300 is known to play the key role in the HIF-1 pathway. However, to date very few compounds have been reported to disrupt HIF-1α/p300 complex. We have rationally designed and synthesized non-peptidic mimics of HIF-1α CTAD αA-helix with novel oligooxopiperazine backbone (OOPs). These mimics exhibit relatively low toxicity and substantially downregulate expression levels of selected hypoxia-inducible genes (VEGF, c-MET, LOX, GLUT1, CXCR4) in cellulo in a dose-dependent manner.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 283. doi:1538-7445.AM2012-283