Casdatifan

**Semantic type:** Pharmacologic Substance

**Definition:** An orally bioavailable allosteric inhibitor of hypoxia inducible factor (HIF)-2alpha, with potential antineoplastic activity. Upon oral administration, casdatifan targets and allosterically binds to a hydrophobic pocket on HIF-2alpha leading to a confirmational change that prevents HIF-2alpha heterodimerization with HIF-1beta and binding to the hypoxia response element (HRE) binding site on DNA. This results in decreased transcription and expression of HIF-2alpha downstream target genes, many of which regulate tumor cell growth and survival. Blocking HIF-2alpha reduces the proliferation of HIF-2alpha-expressing tumor cells. HIF-2alpha, a heterodimeric transcription factor overexpressed under hypoxic conditions in many cancer cell types, promotes proliferation, progression and metastasis of tumors.

**Synonyms:** - AB 521 - AB-521 - AB521 - CASDATIFAN - HIF-2a Inhibitor AB521 - HIF-2alpha Inhibitor AB521