EPAS1 and renal cell carcinoma: HIF-2α inhibitor AB521 under clinical development by Arcus Biosciences and currently in Phase I trial for RCC targets and allosterically binds to a hydrophobic pocket on HIF-2α, leading to a confirmational change that prevents HIF-2α heterodimerization with HIF-1β and binding to the HRE binding site on DNA, resulting in decreased transcription and expression of HIF-2α downstream target genes, many of which regulate tumor cell growth and survival (63, 64).