HPK1-IN-72
HPK1-IN-72 is an orally active and selective HPK1/MAP4K1 inhibitor with an IC50 of 52.4 nM against human targets. HPK1-IN-72 inhibits HPK1 activation, blocks the negative regulation of T cell receptor signaling, restores T cell receptor signal transduction and enhances T cell function. HPK1-IN-72 suppresses tumor growth, exhibits potent single-agent anti-tumor efficacy, and also produces synergistic effects with anti-PD-1 antibodies or anti-PD-L1/IL-15 immunocytokine prodrugs. HPK1-IN-72 can be used in research related to breast cancer, colorectal cancer and prostate cancer.
For research use only. We do not sell to patients.
- CAS No.: 2965385-11-7
- Formula: C25H26N4O4S
- Molecular Weight:478.56
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Biological Activity
Description
IC50 & Target
[1]|
HPK1 52.4 nM (IC50) |
In Vitro
HPK1-IN-72 (0.1-1 μM; 24-72 h) increases IL-2 secretion levels in wild-type Jurkat T cells and primary mouse splenocytes via specific inhibition of HPK1; enhances antigen-specific IFN-γ secretion in OT-1 CD8+ T cells stimulated with OVA peptide; and reverses the immunosuppression induced by PGE2 and NECA (HY-103173) by promoting IFN-γ secretion in human primary T cells[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, primary mouse T cells
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Concentration:0.1, 0.3, 1 μM
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Incubation Time:2 h
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Result:Effectively inhibited phosphorylation of SLP-76 in both Jurkat T cells and primary mouse T cells after anti-CD3 stimulation.
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Cell Line:wild-type Jurkat T cells, HPK1-knockout Jurkat T cells, primary mouse splenocytes
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Concentration:0.1, 0.3, 1 μM
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Incubation Time:24 h (Jurkat cells)
72 h (mouse splenocytes) -
Result:Significantly increased IL-2 secretion in wild-type Jurkat T cells and primary mouse splenocytes compared to stimulated controls.
No enhancement of IL-2 secretion was observed in HPK1-knockout Jurkat T cells, confirming target specificity.
A bell-shaped dose-response curve was observed at higher concentrations.
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Cell Line:OT-1 antigen-specific CD8+ T cells
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Concentration:0.1, 0.3, 1 μM
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Incubation Time:72 h
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Result:Significantly increased IFN-γ secretion in OVA peptide-stimulated OT-1 CD8+ T cells.
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Cell Line:human primary T cells
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Concentration:1 μM
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Incubation Time:72 h
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Result:Nearly reversed the immunosuppressive effect of PGE2 and NECA, significantly increasing IFN-γ secretion in human primary T cells.
Parmacokinetics
In Vivo
HPK1‑IN‑72 (50 mg/kg; p.o.; once daily; for 7 consecutive days) inhibits the growth of RM‑1 prostate tumors in C57BL/6J mice, and exerts a synergistic effect when combined with P‑T‑MMP[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 (8-10 weeks old, subcutaneous implantation of 4T1 cells (3 × 105 cells))[1]
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Dosage:27 mg/kg; 50 mg/kg
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Administration:p.o.; daily; 17 days
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Result:Achieved tumor growth inhibition (TGI) rate of 40.9% at 27 mg/kg.
Achieved tumor growth inhibition (TGI) rate of 57.9% at 50 mg/kg.
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Animal Model:Balb/c (8-10 weeks old, subcutaneous implantation of CT26 cells (2.5 × 105 cells))[1]
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Dosage:50 mg/kg
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Administration:p.o.; daily; 11 days
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Result:Exhibited modest antitumor activity as monotherapy.
Produced marked tumor suppression superior to either monotherapy alone when combined with an anti-PD-1 antibody.
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Animal Model:C57BL/6J (8-10 weeks old, subcutaneous implantation of RM-1 cells (5 × 105 cells))[1]
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Dosage:50 mg/kg
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Administration:p.o.; daily; 7 days
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Result:Achieved a tumor growth inhibition (TGI) rate of 52.3% as monotherapy.
Achieved a tumor growth inhibition (TGI) rate of 81.9% when combined with P-T-MMP (anti-PD-L1/IL-15 prodrug).
Chemical Information
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CAS No. 2965385-11-7
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Molecular Weight 478.56
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Formula C25H26N4O4S
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SMILES
OC(C)(C#CC1=CC(COC2=CC(C3=NC4=C(S3)CN(CC4)C(CO)=O)=CN=C2N)=CC=C1)C
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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)
HPK1-IN-72 Related Classifications
HY-187930 Related Classifications
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