Mechanism of Action
WELIREG™ (belzutifan) is an inhibitor of hypoxia-inducible factor 2 alpha (HIF-2α)
Under normal oxygen levels, HIF-2α is targeted for degradation by VHL protein
See the following images for a summary of the mechanism of action for WELIREG

In VHL disease, VHL protein function is impaired while HIF-2α stabilizes.

Lack of functional VHL protein results in accumulation of HIF-2α. HIF-2α translocates into the nucleus and interacts with hypoxia-inducible factor 1 beta (HIF-1β).

This interaction induces expression of downstream genes leading to associated activity.
