| Identification | Back Directory | [Name]
CPI-455 | [CAS]
1628208-23-0 | [Synonyms]
CPI-455
CPI-455, >98%
CPI 455;CPI455
CPI-455(free base)
CPI 455;CPI-455;CPI455
6-Isopropyl-7-oxo-5-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-3-carbonitrile
Pyrazolo[1,5-a]pyrimidine-3-carbonitrile, 4,7-dihydro-6-(1-methylethyl)-7-oxo-5-phenyl- | [Molecular Formula]
C16H14N4O | [MDL Number]
MFCD29921343 | [MOL File]
1628208-23-0.mol | [Molecular Weight]
278.31 |
| Chemical Properties | Back Directory | [Boiling point ]
488.7±55.0 °C(Predicted) | [density ]
1.28±0.1 g/cm3(Predicted) | [storage temp. ]
-20°C | [solubility ]
Soluble in DMSO (up to at least 25 mg/ml) | [form ]
solid | [pka]
-5.10±0.60(Predicted) | [color ]
Off-white | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months. |
| Hazard Information | Back Directory | [Description]
CPI-455 (1628208-23-0) is a potent (IC50?= 10 nM) and selective inhibitor of the lysine demethylase KDM5 (equal inhibition of KDM5A, 5B, 5C).1?CPI-455 reduced the number of drug-tolerant persister cancer cells (DTPs) in a dose-dependent, KDM5-dependent manner in multiple cell lines treated with standard chemotherapy or targeted agents. CPI-455 synergized with 5-aza-2’-deoxycytidine (DAC) to reduce the viability of luminal breast cancer cells?in vitro.2?KDM5 demethylases have recently been shown to repress the immune response to tumors?via?suppression of STING.3 | [Uses]
CPI-455 is a potent KDM5 demethylase inhibitor. | [in vivo]
Dual blockade of B7-H4 and KDM5B (CPI-455, 50/70 mg/kg, ip, daily) in mice elicits protective immunity[2]. | Animal Model: | Six-week-old male C57BL/6 mice (One- to 2-mm fragments of P. gingivalis–positive PDXs were implanted subcutaneously into the flank region of humanized mice.) | | Dosage: | 50 mg/kg or 70 mg/kg (combined with anti–B7-H4). | | Administration: | IP, daily, 14-28 days. | | Result: | Histopathology analysis revealed no inflammation in either group at 2 weeks in response to the primary infection. However, at 8 weeks after inoculation, mice receiving monotherapy exhibited mild inflammation, whereas the combined treatment presented with heavy to severe inflammation, which persisted at 12 and 16 weeks after challenge.
Treatment with CPI-455 to selectively target H3K4-specific JmjC demethylases increased CXCL11, CXCL9, and CXCL10 following infection, with maximum levels observed 48 hours after infection.
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| [IC 50]
KDM5 | [References]
1) Vinogradova?et al.?(2016),?An inhibitor of KDM5 demethylases reduces survival of drug-tolerant cancer cells;?Nat. Chem. Biol.?12?531
2) Leadem?et al.?(2018),?A KDM5 Inhibitor Increases Global H3K4 Trimethylation Occupancy and Enhances the Biological Efficacy of 5-Aza-2’-Deoxycytidine;?Cancer Res.?78?1127
3) Wu?et al.?(2018),?KDM5 histone demethylases repress immune response via suppression of STING;?PLoS Biol.?16?e2006134dfd |
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