Hypoxia inducible factor down-regulation, cancer and cancer stem cells (CSCs): ongoing success stories

Area of Science:

• Oncology
• Medicinal Chemistry
• Molecular Biology

Background:

• Hypoxia-inducible factor 1 (HIF-1) is over-expressed in cancers, regulating genes vital for tumor growth, metastasis, and cancer stem cells (CSCs).
• HIF-1 is a validated therapeutic target in oncology, with numerous modulators in clinical development.

Purpose of the Study:

• To review recent advances in understanding HIF-1 regulation and inhibition from a medicinal chemist's perspective.
• To highlight small molecules, pseudopeptides, and nano-drugs targeting HIF-1 and CSCs.

Main Methods:

• Literature review focusing on recent scientific publications.
• Selection of "hit" compounds with demonstrated anti-HIF-1 and anti-tumor activities.
• Emphasis on compounds targeting CSCs where possible.

Main Results:

• Identification of diverse small-sized organic molecules, pseudopeptides, and nano-drugs as HIF-1 inhibitors.
• Demonstration of in vitro and/or in vivo anti-HIF-1 and anti-tumor activities for selected compounds.
• Highlighting of compounds with selective activity against CSCs.

Conclusions:

• Medicinal chemistry efforts have yielded promising HIF-1 inhibitors with potential anti-cancer applications.
• Targeting HIF-1, particularly in CSCs, remains a critical strategy in oncology drug development.
• Further research into novel HIF-1 modulators, including nano-drugs, is warranted.