Novel anticancer drug discovery strategies targeting hypoxia-inducible factors

IntroductionHypoxia is a key feature of solid tumors, associated with aggressive behaviors such as radiation and chemotherapy resistance, increased metastasis, and poor prognosis. Hypoxia-inducible factors (HIFs) are essential transcription factors that help tumor cells adapt to hypoxic environments by promoting the expression of pro-oncogenic genes. Reducing HIF activity presents a promising strategy for advancing cancer treatment.Area CoveredIn this paper, the authors present an overview of recent studies on the development of HIF-1/2 inhibitors as potential anticancer drugs. The article offers a comprehensive analysis of the structural characteristics of these inhibitors and explores their relationship with anticancer activity, focusing on research conducted over the past decade, from 2015 to 2024.Expert opinionBecause they play a big role in medicinal chemistry and the discovery of anticancer drugs, HIF inhibitors have always gotten a lot of attention and have been used to make a lot of important molecules with different biological effects, especially in the field of cancer research. Several techniques and chemical scaffolds have successfully targeted HIF-1 alpha. However, additional research is required to sustain HIF-1 alpha inhibition while maintaining anticancer activity. The FDA approval of Belzutifan provided researchers with an opportunity to conduct broader HIF-2 studies.