HPK1-IN-69 

HPK1-IN-69 is an orally active HPK1 inhibitor with an IC₅₀ of 1.7 nM. HPK1-IN-69 inhibits the HPK1-mediated TCR signaling pathway, reduces the phosphorylation level of SLP76, and promotes the release of IL-2. HPK1-IN-69 exhibits in vivo anti-tumor activity in mouse models. HPK1-IN-69 can be used for the research of colorectal cancer and MC38 syngeneic tumors^[1].

HPK1-IN-69 (compound 53) (0-300 nM; 2 h pre-incubation) inhibits CD3/CD28-induced phosphorylation of SLP76 in Jurkat T cells in a dose-dependent manner, with an IC₅₀ of 23.1 nM for pSLP76^[1].
HPK1-IN-69 (0-1000 nM; 1 h pre-incubation) dose-dependently enhances CD3/CD28-induced IL-2 release in Jurkat T cells (EC₅₀ = 29.9 nM) and hPBMCs, and reverses PGE₂-mediated inhibition of IL-2^[1].
HPK1-IN-69 (0-60 min) exhibits favorable metabolic stability in mouse and human liver microsomes, with a half-life of over 30 min^[1].
HPK1-IN-69 exhibits weak inhibitory effects on human CYP isoenzymes, with IC₅₀ values ranging from 6.1 μM to >50 μM, suggesting that it has a specific safety window regarding CYP interactions^[1].
HPK1-IN-69 exhibits relatively low inhibitory activity against hERG channels, with an IC₅₀ of 7.92 μM, suggesting a low risk of cardiotoxicity^[1].

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

HPK1-IN-69 (15-30 mg/kg; i.p.; twice daily; for 17 consecutive days) exhibits dose-dependent antitumor efficacy in the CT26 colorectal cancer mouse model^[1].
HPK1-IN-69 (15-60 mg/kg; i.p./p.o.; twice daily; for 21 consecutive days) exhibits potent anti-tumor efficacy in the MC38 colorectal cancer mouse model, with a tumor growth inhibition (TGI) rate of 64% at the oral dose of 60 mg/kg; it also shows synergistic activity in combination with anti-PD-1 antibody, achieving a TGI of 77%^[1].

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

416.48

C₂₂H₂₄N₈O

3095423-83-6

CN1CCN(CC1)C2=CC=C(C=C2C#N)C3=CN=C(N)C(OCC4=CC=NC(N)=C4)=N3

Room temperature in continental US; may vary elsewhere.

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

• [1]. Duan Y, et al. Discovery of Novel HPK1 Inhibitors via Chemistry-Based Direct-to-Bioassay Screening and SAR Optimization. J Med Chem. 2026 Mar 26;69(6):6736-6759.