Recently, selective HIF-2α allosteric inhibitors PT2385 and PT2977, which weaken heterodimerization with HIF-1β by selectively binding to HIF-2α-PAS-B domain [287], showed 66% and 80% of disease control rate and were well tolerated in phase I/II study of renal cell carcinomas (RCCs) [288,289,290]. Here, EPAS1 is linked to hereditary clear cell renal cell carcinoma.