Casdatifan — Investigational Agent
HIF-2α Inhibitor · Phase 1/2 · Arcus Biosciences
Mechanism of Action
Potent, selective small-molecule inhibitor of hypoxia-inducible factor 2-alpha (HIF-2α). In clear cell RCC, near-universal VHL loss stabilizes HIF-2α, driving transcription of VEGF, cyclin D1, and other pro-tumorigenic genes. Casdatifan binds the HIF-2α PAS-B domain, preventing HIF-2α/HIF-1β heterodimerization and downstream oncogenic transcription. It is designed for higher target coverage than the approved HIF-2α inhibitor belzutifan.
Investigational Indications
- Advanced clear cell renal cell carcinoma (ccRCC)
- Other HIF-2α–dependent solid tumors