| Identification | Back Directory | [Name]
1(3H)-Isobenzofuranone, 5-[[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-5-(1,3,4-oxadiazol-2-yl)-2-pyrimidinyl]amino]-3,3-dimethyl- | [CAS]
2320462-65-3 | [Synonyms]
HPK1-IN-7
HPK1 IN 7,MC38,Inhibitor,PD1,HPK1IN7,tumor,model,oral,selectivity,HPK-1-IN-7,MAP4K,inhibit,MAPK Kinase Kinase Kinase
1(3H)-Isobenzofuranone, 5-[[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-5-(1,3,4-oxadiazol-2-yl)-2-pyrimidinyl]amino]-3,3-dimethyl- | [Molecular Formula]
C24H22N6O4 | [MDL Number]
MFCD34476053 | [MOL File]
2320462-65-3.mol | [Molecular Weight]
458.47 |
| Chemical Properties | Back Directory | [Boiling point ]
754.3±70.0 °C(Predicted) | [density ]
1.404±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 125 mg/mL (272.65 mM; Need ultrasonic) | [form ]
Solid | [pka]
14.22±0.10(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
HPK1-IN-7 is a potent, orally active HPK1 (hematopoietic progenitor kinase 1, MAP4K1) inhibitor (IC50=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-PD1[1]. | [in vivo]
HPK1-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[1].
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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 AUC0-24h was 19 μM?h. The calculated oral bioavailability based on these pharmacokinetics studies is approximately 100%[1]. | Animal Model: | Mice (MC38 syngeneic tumor model)[1] | | 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. |
| [IC 50]
HPK1: 2.6 nM (IC50); GLK/MAP4K3: 140 nM (IC50); IRAK4: 59 nM (IC50); Fms/CSFR: 3.2 nM (IC50); FLT3: 25.4 nM (IC50); AMPKA1: 44.3 nM (IC50); cKIT: 45.7 nM (IC50); MST1: 55.1 nM (IC50); ICK: 65.1 nM (IC50); MST2: 78.5 nM (IC50) | [storage]
Store at -20°C | [References]
[1] Degnan AP, et al. Discovery of Orally Active Isofuranones as Potent, Selective Inhibitors of Hematopoetic Progenitor Kinase 1. ACS Med Chem Lett. 2021;12(3):443-450. Published 2021 Feb 19. DOI:10.1021/acsmedchemlett.0c00660 |
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| Company Name: |
InvivoChem
|
| Tel: |
13549236410 |
| Website: |
https://www.invivochem.cn/ |
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