HPK1-IN-52 is an effective orally active hematopoietic progenitor kinase 1 (HPK1) inhibitor, displaying anti-tumor activity with an IC50 value of 10.4 nM.

MAP4K4:665 nM, MAP4K5:104 nM, HPK1:10.4 nM, GLK/MAP4K3:85 nM, MAP4K2:448 nM, MAP4K6:168 nM

HPK1-IN-52 (compound 24) exhibits significant activity (IC 50 of 10.4 nM) and cellular potency (pSLP76 EC 50 of 41 nM and IL-2 EC 50 of 108 nM).

HPK1-IN-52 (compound 24; 30 mg/kg; oral administration; twice daily; for two weeks) demonstrated moderate tumor growth inhibition (TGI) with a TGI of 42%. In mice, HPK1-IN-52 showed significantly increased plasma clearance (Clp = 46 mL/min/kg) and significantly higher oral exposure (AUC (0–24h) = 4139 h ng/mL). Additionally, in rats, this compound exhibited a lower in vivo clearance rate (Clp = 67 mL/min/kg) and higher oral exposure (AUC (0–24h) = 2013 h ng/mL).