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.
For research use only. We do not sell to patients.
- CAS No.: 3095423-83-6
- Formula: C22H24N8O
- Molecular Weight:416.48
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Biological Activity
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HPK1 |
IL-2 |
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.
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Cell Line:Jurkat T cells
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Concentration:0, 1, 3, 10, 30, 100, 300 nM
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Incubation Time:2 h (pre-incubation prior to 10 min CD3/CD28 stimulation)
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Result:Dose-dependently inhibited SLP76 phosphorylation in Jurkat cells, with a cellular IC50 of 23.1 nM for pSLP76 inhibition.
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.
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Animal Model:BALB/c (female, 18-22 g, 4-5 weeks old, subcutaneous inoculation of CT26 cells)[1]
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Dosage:15 mg/kg; 30 mg/kg; 30 mg/kg
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Administration:i.p.; twice daily; 17 days
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Result:Achieved a tumor growth inhibition (TGI) rate of 36% at 15 mg/kg.
Achieved a TGI of 62% at 30 mg/kg, with significantly reduced tumor weight relative to the model group.
Achieved a TGI of 75% when combined with anti-PD-1 antibody.
Enhanced CD8+ T-cell infiltration into tumor tissue in a dose-dependent manner.
Caused no significant body weight loss or major organ damage.
Chemical Information
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CAS No. 3095423-83-6
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Molecular Weight 416.48
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Formula C22H24N8O
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SMILES
CN1CCN(CC1)C2=CC=C(C=C2C#N)C3=CN=C(N)C(OCC4=CC=NC(N)=C4)=N3
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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