HS-10516 (Hansoh Pharmaceutical Group)

HS-10516 is an orally bioavailable small molecule inhibitor of hypoxia-inducible factor 2-alpha (HIF-2α), also known as endothelial PAS domain-containing protein 1 (EPAS1). Developed by Jiangsu Hansoh Pharmaceutical, it is primarily being investigated for the treatment of advanced clear cell renal cell carcinoma (ccRCC) and Von Hippel-Lindau (VHL) syndrome-associated tumors. In ccRCC, the loss of the VHL tumor suppressor protein leads to the stabilization and accumulation of HIF-2α, which drives the transcription of genes involved in angiogenesis, cell proliferation, and tumor progression. HS-10516 aims to disrupt this oncogenic signaling pathway by inhibiting the activity of HIF-2α. It is currently in Phase I clinical development in China and is classified as a Category 1 innovative drug.