GCN2 inhibitor 39 is a highly potent and selective, orally active inhibitor of general control nonderepressible 2 (GCN2) with IC50 of 5 nM.
GCN2 inhibitor 39 displays excellent selectivity against its closely related Integrated Stress Response (ISR) family members heme-regulated inhibitor kinase (HRI), PKR, and (PKR)-like endoplasmic reticulum kinase (PERK).
GCN2 inhibitor 39 engages GCN2 at levels ≥80% with an oral dose of 15 mg/kg BID in mice.
GCN2 inhibitor 39 alleviates MDSC-related T cell suppression and restore T cell proliferation, similar to the effect seen in MDSCs from GCN2 knockout mice.
GCN2 inhibitor 39 (50 mg/kg, BID) demonstrates significant tumor growth inhibition (TGI) as a single agent in the LL2 syngeneic mouse model, also enhances TGI mediated by anti-VEGFR.
