1628208-23-0

Basic information

• Product Name: CPI-455
• Synonyms: CPI-455;6-Isopropyl-7-oxo-5-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-3-carbonitrile
• CAS NO: 1628208-23-0
• Molecular Formula: C16H14N4O
• Molecular Weight: 278.30856
• EINECS: -0
• Mol File: 1628208-23-0.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 488.7±55.0 °C(Predicted)
• Appearance: /
• Density: 1.28±0.1 g/cm3(Predicted)
• Storage Temp.: -20°C
• Solubility: Soluble in DMSO (up to at least 25 mg/ml)
• PKA: -5.10±0.60(Predicted)
• 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.
• CAS DataBase Reference: CPI-455(CAS DataBase Reference)
• NIST Chemistry Reference: CPI-455(1628208-23-0)
• EPA Substance Registry System: CPI-455(1628208-23-0)

Safety Data

• Hazardous Substances Data: 1628208-23-0(Hazardous Substances Data)

Usage

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.

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

Upstream product

• 25491-47-8 2-benzoyl-3-methyl-butyric acid ethyl ester 
• 16617-46-2 3-amino-4-cyano-2H-pyrazole 
• 672323-30-7 7-oxo-5-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-3-carbonitrile 
• 94-02-0 ethyl 3-oxo-3-phenylpropionate 

Relevant articles and documents

Lead optimization of a pyrazolo[1,5-a]pyrimidin-7(4H)-one scaffold to identify potent, selective and orally bioavailable KDM5 inhibitors suitable for in vivo biological studies

Starting with a lead [1,5-a]pyrimidin-7(4H)-one-containing molecule (1), we generated potent, selective and orally bioavailable KDM5 inhibitors. Using structure- and property-based approaches, we designed 48 with improved cell potency (PC9 H3K4Me3 EC50?=?0.34?μM). Furthermore, 48 maintained suitable physiochemical properties and displayed an excellent pharmacokinetic (PK) profile in mice. When dosed orally in mice at 50?mg/kg twice a day (BID), 48 showed an unbound maximal plasma concentration (Cmax) >15-fold over its cell EC50, thereby providing a robust chemical probe for studying KDM5 biological functions in vivo.

THERAPEUTIC COMPOUNDS AND USES THEREOF

The present invention relates to compounds useful as inhibitors of one or more histone demethylses, such as KDM5. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said