1628208-23-0 Usage
Description
CPI-455, also known as 1628208-23-0, is a potent and selective inhibitor of the lysine demethylase KDM5, which includes equal inhibition of KDM5A, 5B, and 5C. It has demonstrated the ability to reduce the number of drug-tolerant persister cancer cells (DTPs) in a dose-dependent and KDM5-dependent manner across various cell lines treated with standard chemotherapy or targeted agents. Additionally, CPI-455 has shown synergistic effects when combined with 5-aza-2'-deoxycytidine (DAC) to reduce the viability of luminal breast cancer cells in vitro. KDM5 demethylases have been found to repress the immune response to tumors by suppressing STING.
Uses
Used in Oncology:
CPI-455 is used as a potent KDM5 demethylase inhibitor for targeting and reducing the number of drug-tolerant persister cancer cells (DTPs) in multiple cell lines. Its application aids in enhancing the effectiveness of standard chemotherapy or targeted agents, making it a valuable tool in the fight against cancer.
Used in Combination Therapy:
CPI-455 is used in combination therapy with 5-aza-2'-deoxycytidine (DAC) to reduce the viability of luminal breast cancer cells in vitro. This synergistic effect enhances the chemo-sensitivity and efficacy of the treatment, particularly in resistant cases.
Used in Immune Response Modulation:
CPI-455 is used to modulate the immune response to tumors by inhibiting KDM5 demethylases, which have been shown to suppress the STING pathway. This application can potentially improve the body's natural defense mechanisms against cancer cells.
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
Check Digit Verification of cas no
The CAS Registry Mumber 1628208-23-0 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,6,2,8,2,0 and 8 respectively; the second part has 2 digits, 2 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 1628208-23:
(9*1)+(8*6)+(7*2)+(6*8)+(5*2)+(4*0)+(3*8)+(2*2)+(1*3)=160
160 % 10 = 0
So 1628208-23-0 is a valid CAS Registry Number.
1628208-23-0Relevant 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
Liang, Jun,Zhang, Birong,Labadie, Sharada,Ortwine, Daniel F.,Vinogradova, Maia,Kiefer, James R.,Gehling, Victor S.,Harmange, Jean-Christophe,Cummings, Richard,Lai, Tommy,Liao, Jiangpeng,Zheng, Xiaoping,Liu, Yichin,Gustafson, Amy,Van der Porten, Erica,Mao, Weifeng,Liederer, Bianca M.,Deshmukh, Gauri,Classon, Marie,Trojer, Patrick,Dragovich, Peter S.,Murray, Lesley
, p. 4036 - 4041 (2016)
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
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Page/Page column 69, (2015/10/05)
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
