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HC-7366 is a first-in-class, orally bioavailable small molecule activator of the GCN2 (general control nonderepressible 2) kinase, also known as EIF2AK4. Developed by HiberCell, HC-7366 works by hyperactivating the GCN2 pathway, which triggers the integrated stress response (ISR) in tumor cells. This mechanism leads to the phosphorylation of eIF2α, resulting in the inhibition of general protein translation, cell cycle arrest, suppression of hypoxia-inducible factor (HIF), and the induction of apoptosis. HC-7366 is currently being evaluated in Phase 1 clinical trials for the treatment of various advanced solid tumors, including head and neck squamous cell carcinoma (HNSCC), colorectal cancer (CRC), and renal cell carcinoma (RCC), where it is being studied both as a monotherapy and in combination with agents such as the HIF-2α inhibitor belzutifan.
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