| Identification | Back Directory | [Name]
Benzeneacetamide, α-[[(2S)-2-(4-cyanophenyl)propyl]amino]-N-[5-(1-methyl-1H-pyrazol-4-yl)-2-pyridinyl]-, (αR)- | [CAS]
2374971-81-8 | [Synonyms]
CPI-1612
Benzeneacetamide, α-[[(2S)-2-(4-cyanophenyl)propyl]amino]-N-[5-(1-methyl-1H-pyrazol-4-yl)-2-pyridinyl]-, (αR)- | [Molecular Formula]
C27H26N6O | [MDL Number]
MFCD32899894 | [MOL File]
2374971-81-8.mol | [Molecular Weight]
450.55 |
| Chemical Properties | Back Directory | [Boiling point ]
719.1±60.0 °C(Predicted) | [density ]
1.20±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 100 mg/mL (221.96 mM; Need ultrasonic) | [form ]
Solid | [pka]
12.12±0.70(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
CPI-1612 is a highly potent, orally active EP300/CBP histone acetyltransferase (HAT) inhibitor with an IC50 of 8.1 nM for EP300 HAT. CPI-1612 has an anticancer activity[1]. | [in vivo]
CPI-1612 (compound 17; 0.5 mg/kg; oral administration; twice a day; for 4 weeks) treatment shows 67% tumor growth inhibition (TGI) with concomitant reduction of H3K27Ac in plasma and reduction of H3K18Ac in the tumor[1].
While the oral exposure of CPI-1612 (compound 17) in dogs (0.5 mg/kg IV; 1.0 mg/kg PO; clearance = 0.42 L/h/kg, Vss = 3.7 L/kg, T1/2 = 5.5 h, F% = 71; AUC/dose = 1691 h·mg/mL) and mice (1 mg/kg IV; 5 mg/kg PO; clearance = 3.8 L/h/kg, Vss = 2.0 L/kg, T1/2 = 0.98 h, F% = 79; AUC/dose = 211 h·mg/mL) is good, the exposure in rats is limited by poor bioavailability (1.0 mg/kg IV; 5.0 mg/kg PO; clearance = 2.6 L/h/kg, Vss = 1.8 L/kg, T1/2 = 1.2 h, F% = 9; AUC/dose = 35.6 h·mg/mL)[1].
A single dose of CPI-1612 is administered orally to CD-1 mice and brain and plasma exposures of CPI-1612 are measured at 0.25, 0.5, 1.0, 2.0, 4.0, and 8.0 h. CPI-1612 is highly brain-penetrant, showing a brain-to-plasma ratio of 0.35 after a single oral dose[1]. | Animal Model: | C57B6 mice injected with JEKO-1 cells[1] | | Dosage: | 0.5 mg/kg | | Administration: | Oral administration; twice a day; for 4 weeks | | Result: | Showed 67% tumor growth inhibition (TGI) at a dose of 0.5 mg/kg. |
| [IC 50]
CBP/p300 | [References]
[1] Jonathan E Wilson, et al. Discovery of CPI-1612: A Potent, Selective, and Orally Bioavailable EP300/CBP Histone Acetyltransferase Inhibitor. ACS Med Chem Lett. 2020 Apr 23;11(6):1324-1329. DOI:10.1021/acsmedchemlett.0c00155 |
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