1621862-70-1 Usage
Biological Activity
0.002 μm for biochemical ic50; 0.032 μm for cellular ec50.cpi-1205 is an ezh2 inhibitor.polycomb repressive complex 2 (prc2) plays a key role in transcriptional silencing partially by installing methylation marks on lysine 27 of histone 3. dysregulation of prc2 function relates with certain malignancies and poor prognosis. ezh2 is thus representing a promising candidate oncology target for pharmacological intervention.
in vitro
previous study reported that the treatment with cpi-1205 caused apoptosis in multiple myeloma and plasmacytoma cell models. cpi-1205 also had a clean selectivity profile when tested against 30 other histone or dna methyltransferases. in addition, cpi-1205 demonstrated modest selectivity when tested against enhancer of zeste homologue 1 (ezh1) that is a methyltransferase highly related to ezh2 [1].
in vivo
in animal study, cpi-1205 was dosed at 160 mg/kg orally twice daily for 25 days in tumor bearing female cb-17 scid mice. by the treatment of tumor-bearing mice with cpi-1205, tumor regression was observed within two weeks. by the end of day 25, significant tumor growth inhibition was recorded. cpi-1205 was found to be well-tolerated for repeat dosing as observed by the absence of significant body weight loss. in addition, analysis of plasma and tumor at 1 h post last dose on day 25 showed sufficient plasma and tumor tissue concentrations [1].
references
[1] vaswani rg et al. identification of (r)-n-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1h-indole-3-carboxamide (cpi-1205), a potent and selective inhibitor of histone methyltransferase ezh2, suitable for phase i
Check Digit Verification of cas no
The CAS Registry Mumber 1621862-70-1 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,6,2,1,8,6 and 2 respectively; the second part has 2 digits, 7 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 1621862-70:
(9*1)+(8*6)+(7*2)+(6*1)+(5*8)+(4*6)+(3*2)+(2*7)+(1*0)=161
161 % 10 = 1
So 1621862-70-1 is a valid CAS Registry Number.
1621862-70-1Relevant articles and documents
SYNTHESIS OF INHIBITORS OF EZH2
-
, (2018/05/16)
Provided herein are synthetic methods for the preparation of EZH2 inhibitors.
Identification of (R)-N-((4-Methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1H-indole-3-carboxamide (CPI-1205), a Potent and Selective Inhibitor of Histone Methyltransferase EZH2, Suitabl
Vaswani, Rishi G.,Gehling, Victor S.,Dakin, Les A.,Cook, Andrew S.,Nasveschuk, Christopher G.,Duplessis, Martin,Iyer, Priyadarshini,Balasubramanian, Srividya,Zhao, Feng,Good, Andrew C.,Campbell, Robert,Lee, Christina,Cantone, Nico,Cummings, Richard T.,Normant, Emmanuel,Bellon, Steven F.,Albrecht, Brian K.,Harmange, Jean-Christophe,Trojer, Patrick,Audia, James E.,Zhang, Ying,Justin, Neil,Chen, Shuyang,Wilson, Jon R.,Gamblin, Steven J.
, p. 9928 - 9941 (2016/11/19)
Polycomb repressive complex 2 (PRC2) has been shown to play a major role in transcriptional silencing in part by installing methylation marks on lysine 27 of histone 3. Dysregulation of PRC2 function correlates with certain malignancies and poor prognosis
MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF
-
Paragraph 00316; 00317, (2013/08/28)
Agents for modulating methyl modifying enzymes, compositions and uses thereof are provided herein.
