1446144-04-2 Usage
Description
CPI-203 is a primary amide analog of (+)-JQ1, which has shown superior bioavailability with oral or i.p. administration. CPI-203 downregulates Myc expression, causes G1 cell cycle arrest and attenuates cell proliferation in human pancreatic neuroendocrine tumors. CPI-203 also arrests the growth of T cell acute lymphoblastic leukemia cells in vitro (EC50 = 91.2 nM).
Uses
CPI-203 is a bromodomain and extraterminal domain (BET) inhibitor.
Biological Activity
cpi-203 is a potent, selectivie and competitive small molecule inhibitor of bet bromodomain with a mean gi50 value of 0.23μm in mcl cell lines [1].as an inhibitor of bet proteins, cpi-203 inhibits brd4 in vitro and in cells. it inhibits the specific ser2 phosphorylation of both endogenous brd4 and exogenous mutant brd4 (brd4 fee-aaa) in vivo, thus blocking the recruitment of brd4 to chromatin. cpi-203 is shown to suppress cell growth of 9 mcl cell lines. and in rec-1 cells, treatment of cpi-203 causes the effects of irf4 expression. cpi-203 marginally activates the apoptotic program in these cells. the cpi-203-lenalidomide combination is reported to be a promising strategy in mcl cases refractory to proteasome inhibition [1, 2].
references
[1] moros a, rodríguez v, saborit-villarroya i, montraveta a, balsas p, sandy p, martínez a, wiestner a, normant e, campo e, pérez-galán p, colomer d, roué g. synergistic antitumor activity of lenalidomide with the bet bromodomain inhibitor cpi203 in bortezomib-resistant mantle cell lymphoma. leukemia. 2014 mar 18.[2] devaiah bn, lewis ba, cherman n, hewitt mc, albrecht bk, robey pg, ozato k, sims rj 3rd, singer ds. brd4 is an atypical kinase that phosphorylates serine2 of the rna polymerase ii carboxy-terminal domain. proc natl acad sci u s a. 2012 may 1;109(18):6927-32.
Check Digit Verification of cas no
The CAS Registry Mumber 1446144-04-2 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,4,4,6,1,4 and 4 respectively; the second part has 2 digits, 0 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 1446144-04:
(9*1)+(8*4)+(7*4)+(6*6)+(5*1)+(4*4)+(3*4)+(2*0)+(1*4)=142
142 % 10 = 2
So 1446144-04-2 is a valid CAS Registry Number.
1446144-04-2Relevant articles and documents
Antibody-Mediated Delivery of Chimeric BRD4 Degraders. Part 1: Exploration of Antibody Linker, Payload Loading, and Payload Molecular Properties
Dragovich, Peter S.,Pillow, Thomas H.,Blake, Robert A.,Sadowsky, Jack D.,Adaligil, Emel,Adhikari, Pragya,Bhakta, Sunil,Blaquiere, Nicole,Chen, Jinhua,Dela Cruz-Chuh, Josefa,Gascoigne, Karen E.,Hartman, Steven J.,He, Mingtao,Kaufman, Susan,Kleinheinz, Tracy,Kozak, Katherine R.,Liu, Liang,Liu, Liling,Liu, Qi,Lu, Ying,Meng, Fanwei,Mulvihill, Melinda M.,O'Donohue, Aimee,Rowntree, Rebecca K.,Staben, Leanna R.,Staben, Steven T.,Wai, John,Wang, Jian,Wei, Binqing,Wilson, Catherine,Xin, Jianfeng,Xu, Zijin,Yao, Hui,Zhang, Donglu,Zhang, Hongyan,Zhou, Hao,Zhu, Xiaoyu
, p. 2534 - 2575 (2021/03/09)
The biological and medicinal impacts of proteolysis-targeting chimeras (PROTACs) and related chimeric molecules that effect intracellular degradation of target proteins via ubiquitin ligase-mediated ubiquitination continue to grow. However, these chimeric entities are relatively large compounds that often possess molecular characteristics, which may compromise oral bioavailability, solubility, and/or in vivo pharmacokinetic properties. We therefore explored the conjugation of such molecules to monoclonal antibodies using technologies originally developed for cytotoxic payloads so as to provide alternate delivery options for these novel agents. In this report, we describe the first phase of our systematic development of antibody-drug conjugates (ADCs) derived from bromodomain-containing protein 4 (BRD4)-targeting chimeric degrader entities. We demonstrate the antigen-dependent delivery of the degrader payloads to PC3-S1 prostate cancer cells along with related impacts on MYC transcription and intracellular BRD4 levels. These experiments culminate with the identification of one degrader conjugate, which exhibits antigen-dependent antiproliferation effects in LNCaP prostate cancer cells.