HPK1-IN-7 (C09-1138-550)

HPK1-IN-7 is a potent, orally active HPK1 (hematopoietic progenitor kinase 1, MAP4K1) inhibitor ( IC 50 =2.6 nM) with excellent family and kinome selectivity. HPK1-IN-7 shows selectivity against IRAK4 (59 nM) and GLK (140 nM). HPK1-IN-7 shows robust efficacy against MC38 syngeneic tumor model in combination with anti-PD1In VivoHPK1-IN-7 (100 mg/kg; p.o.; twice daily for 28 days) shows robust enhancement of anti-PD1 efficacy in a syngeneic tumor model of colorectal cancer . HPK1-IN-7 (compound 24) (1 mg/kg; intravenous; mice) is characterized by moderate plasma clearance (43 mL/min/kg) and a large volume of distribution (4.4 L/kg). After oral administration (20 mg/kg), the Cmax was 5.3 μM and the AUC 0-24h was 19 μM•h. The calculated oral bioavailability based on these pharmacokinetics studies is approximately 100% . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Mice (MC38 syngeneic tumor model) Dosage: 100 mg/kg Administration: Oral; twice daily for 28 days Result: Enhanced the efficacy of anti-PD1 treatment, garnering a 100% cure rate vs a 20% cure rate with anti-PD1 alone.IC50& Target:HPK1 2.6 nM (IC 50 ) GLK/MAP4K3 140 nM (IC 50 ) IRAK4 59 nM (IC 50 ) Fms/CSFR 3.2 nM (IC 50 ) FLT3 25.4 nM (IC 50 ) AMPKA1 44.3 nM (IC 50 ) cKIT 45.7 nM (IC 50 ) MST1 55.1 nM (IC 50 ) ICK 65.1 nM (IC 50 ) MST2 78.5 nM (IC 50 ). Specification: 10mM in DMSO Molecular Formula: C24H22N6O4 Molecular Weight: 458.5