AZ3246 

AZ3246 is an orally active and selective inhibitor of HPK1 with an IC₅₀ < 3 nM. AZ3246 induces IL-2 secretion in T cells with an EC₅₀ of 90 nM. AZ3246 is a low-volume, low-clearance antitumor compound^[1].

AZ3246 (100 nM) is highly selective for HPK1 over STK3, STK4, and TNIK , hits only HPK1 and MYLK at >80% inhibition, hits ROS1, YSK4 and TNIK at >50% inhibition^[1].
AZ3246 has excellent metabolic stability in human liver microsomes^[1].
AZ3246 induces IL-2 secretion in T cells with an EC₅₀ of 90 nM without inhibiting antagonistic kinases^[1].
AZ3246 exhibits low CL_int values in primary human, rat, and dog hepatocytes. Low turnover was also observed in HμREL cocultures for rat, dog, monkey, and human hepatocytes^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

AZ3246 (30 mg/kg; p.o.; twice daily) inhibits tumor growth in EMT6 mouse model，AZ3246 (30-150 mg/kg) shows no effect on animal bodyweight ^[1].
AZ3246 (10-100 mg/kg; p.o.) exposure in mouse is linear up to 30 mg/kg with a limited increase in exposure at 100 mg/kg^[1].
AZ3246 is a low-volume, low-clearance compound, consistent with a neutral molecule that is not heavily metabolized by the liver^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

471.44

C₂₁H₂₀F₃N₉O

2893978-54-4

FC(F)(CN1N=C(C)C(NC2=C(C(N)=O)N=C(C3=CN=CC4=C3N=CN4C)C(C5CC5)=N2)=C1)F

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Shields JD, et al. Discovery and Optimization of Pyrazine Carboxamide AZ3246, a Selective HPK1 Inhibitor. J Med Chem. 2025 Feb 27;68(4):4582-4595.  [Content Brief]