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.
Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.
- CAS. Nr.: 2965385-11-7
- Formel: C25H26N4O4S
- Molecular Weight:478.56
-
Speicherung:
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]
-
Biologische Aktivität
-
Chemical Information
- Reinheit & Dokumentation
- Verweise
-
Help & FAQs
Alle MAP4K Isoform-spezifische Produkte anzeigen
More
Biologische Aktivität
Beschreibung
IC50 & Target
[1]|
HPK1 52.4 nM (IC50) |
In Vitro
HPK1-IN-72 (compound 23) potently inhibits purified HPK1 kinase, with an IC50 of 52.4 nM; it exhibits 20- to 190-fold higher selectivity for HPK1 over the MAP4K family kinases GCK, GLK and HGK, with a selectivity of over 190-fold against GLK; when tested against a kinome panel consisting of 109 human kinases, it inhibits HPK1 and four additional kinases (VEGFR3, RET, CSF1R, KHS) by more than 90%[1].
HPK1-IN-72 (0.1-1 μM; 2 h) inhibits the phosphorylation of SLP-76 in Jurkat T cells and primary mouse T cells, confirming its ability to inhibit HPK1 at the cellular level[1].
HPK1-IN-72 (0.1-1 μM; 24 h) dose-dependently enhances NFAT-driven luciferase activity in Jurkat-Lucia NFAT reporter cells co-stimulated with PMA (HY-18739) and Ionomycin (HY-13434), thereby potentiating the TCR signaling pathway[1].
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.
-
Cell Line:Jurkat T cells, primary mouse T cells
-
Concentration:0.1, 0.3, 1 μM
-
Incubation Time:2 h
-
Result:Effectively inhibited phosphorylation of SLP-76 in both Jurkat T cells and primary mouse T cells after anti-CD3 stimulation.
-
Cell Line:wild-type Jurkat T cells, HPK1-knockout Jurkat T cells, primary mouse splenocytes
-
Concentration:0.1, 0.3, 1 μM
-
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.
-
Cell Line:OT-1 antigen-specific CD8+ T cells
-
Concentration:0.1, 0.3, 1 μM
-
Incubation Time:72 h
-
Result:Significantly increased IFN-γ secretion in OVA peptide-stimulated OT-1 CD8+ T cells.
-
Cell Line:human primary T cells
-
Concentration:1 μM
-
Incubation Time:72 h
-
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 11 consecutive days) shows only moderate activity against CT26 colon tumors in Balb/c mice, but combination treatment with anti‑PD‑1 antibody exerts a synergistic effect to enhance anti‑tumor efficacy[1].
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.
-
Animal Model:Balb/c (8-10 weeks old, subcutaneous implantation of 4T1 cells (3 × 105 cells))[1]
-
Dosage:27 mg/kg; 50 mg/kg
-
Administration:p.o.; daily; 17 days
-
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.
-
Animal Model:Balb/c (8-10 weeks old, subcutaneous implantation of CT26 cells (2.5 × 105 cells))[1]
-
Dosage:50 mg/kg
-
Administration:p.o.; daily; 11 days
-
Result:Exhibited modest antitumor activity as monotherapy.
Produced marked tumor suppression superior to either monotherapy alone when combined with an anti-PD-1 antibody.
-
Animal Model:C57BL/6J (8-10 weeks old, subcutaneous implantation of RM-1 cells (5 × 105 cells))[1]
-
Dosage:50 mg/kg
-
Administration:p.o.; daily; 7 days
-
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
-
CAS. Nr. 2965385-11-7
-
Molecular Weight 478.56
-
Formel C25H26N4O4S
-
SMILES
OC(C)(C#CC1=CC(COC2=CC(C3=NC4=C(S3)CN(CC4)C(CO)=O)=CN=C2N)=CC=C1)C
-
Versand
Room temperature in continental US; may vary elsewhere.
-
Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Reinheit & Dokumentation
Verweise
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
HPK1-IN-72 Related Classifications
HY-187930 Related Classifications
Powered by Bioz