AB521: a small molecule inhibitor of the hypoxic transcriptional regulator HIF-2⍺ that has demonstrated potent antitumor activity in xenograft models of cancer.

HIF-2⍺ is a key transcriptional regulator that helps drive the growth of many solid tumors. HIF-2⍺ is regulated through degradation and is normally only stably expressed and accumulated in cells under hypoxic conditions. Hypoxic tumors correlate highly with upregulation of the adenosine pathway, suggesting that targeting the adenosine pathway may enhance the antitumor activity of AB521. A Phase 1/1b study to explore AB521 in clear-cell renal cell carcinoma, alone and in combination with other molecules, including those targeting the CD73-adenosine axis, is planned.

Activity of HIF-2⍺ and AB521 within the tumor cell nucleus