Advances in inhibition of protein-protein interactions targeting hypoxia-inducible factor-1 for cancer therapy

Bioorganic & Medicinal Chemistry
Jia LiYuyan Li

Abstract

Hypoxia is a common characteristic of many types of solid tumors and is associated with tumor propagation, malignant progression, and resistance to anti-cancer therapy. HIF-1 pathway is one of the survival pathways activated in tumor in response to hypoxia. In hypoxic condition, hypoxia-inducible factor-1α (HIF-1α) is stabilized and translocated into nucleus where it forms heterodimer with HIF-1β and regulates the expression of a plethora of genes involved in different processes, such as cell proliferation, differentiation, apoptosis, vascularization/angiogenesis, tumor invasion and metastasis. Recruitment of co-activator p300 or CBP to HIF-1α is critical to the transactivation activity of HIF-1 dimer, therefore, small molecules which can block the dimerization of HIF-1α and HIF-1β or inhibit the interaction between HIF-1α and p300 can function as inhibitors of HIF-1 and have the potential to be developed as novel therapies for the treatment of human cancers. In this review, recent progress of small molecular inhibitors of protein-protein interactions targeting HIF-1 is summarized, the mechanism of functions of these compounds and their potential usage as anti-cancer agents have also been discussed.

Citations

May 21, 2020·Journal of Computer-aided Molecular Design·Metin Yazar, Pemra Ozbek
Jan 3, 2020·Environmental Geochemistry and Health·Yongya Wu, Lu Kong
Oct 29, 2020·Journal of Experimental & Clinical Cancer Research : CR·Tiansheng LiYongguang Tao
Dec 8, 2020·Oxidative Medicine and Cellular Longevity·Yang LiuYanfeng Wang
Mar 7, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Xinheng HeShaoyong Lu
May 9, 2021·Colloids and Surfaces. B, Biointerfaces·Marhaba MamatSong Shen

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