1446144-04-2 Usage
Description
CPI-203 is a primary amide analog of (+)-JQ1, a bromodomain and extraterminal domain (BET) inhibitor. It has demonstrated superior bioavailability with oral or intraperitoneal (i.p.) administration and is known for its ability to downregulate Myc expression, induce G1 cell cycle arrest, and attenuate cell proliferation in human pancreatic neuroendocrine tumors. Additionally, CPI-203 has been shown to arrest the growth of T cell acute lymphoblastic leukemia cells in vitro.
Uses
Used in Oncology:
CPI-203 is used as an anticancer agent for the treatment of various types of cancer, including pancreatic neuroendocrine tumors and T cell acute lymphoblastic leukemia. It functions by inhibiting the BET proteins, which play a crucial role in the regulation of gene expression and cell proliferation, leading to the suppression of tumor growth and progression.
Used in Drug Development:
CPI-203 is utilized in the development of novel therapeutic strategies for cancer treatment. Its ability to target BET proteins makes it a promising candidate for the development of new drugs that can potentially overcome drug resistance and improve the efficacy of existing cancer treatments.
Used in Research:
CPI-203 serves as a valuable research tool for studying the role of BET proteins in various cellular processes, including cell cycle regulation, gene expression, and cancer development. It can be used to investigate the molecular mechanisms underlying the pathogenesis of different types of cancer and to identify potential therapeutic targets for the development of new cancer treatments.
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.