Identification of a Benzoisoxazoloazepine Inhibitor (CPI-0610) of the Bromodomain and Extra-Terminal (BET) Family as a Candidate for Human Clinical Trials

Journal of Medicinal Chemistry
Brian K AlbrechtJames E Audia

Abstract

In recent years, inhibition of the interaction between the bromodomain and extra-terminal domain (BET) family of chromatin adaptors and acetyl-lysine residues on chromatin has emerged as a promising approach to regulate the expression of important disease-relevant genes, including MYC, BCL-2, and NF-κB. Here we describe the identification and characterization of a potent and selective benzoisoxazoloazepine BET bromodomain inhibitor that attenuates BET-dependent gene expression in vivo, demonstrates antitumor efficacy in an MV-4-11 mouse xenograft model, and is currently undergoing human clinical trials for hematological malignancies (CPI-0610).

References

Oct 19, 2004·Genes & Development·Robert J SimsDanny Reinberg
Oct 9, 2009·Molecular Biology of the Cell·Anup DeyKeiko Ozato
Apr 28, 2010·Chemical Reviews·MaryAnn T RobakJonathan A Ellman
Sep 28, 2010·Nature·Panagis FilippakopoulosJames E Bradner
Nov 12, 2010·Nature·Edwige NicodemeAlexander Tarakhovsky
Aug 5, 2011·Nature·Johannes ZuberChristopher R Vakoc
Sep 6, 2011·Cell·Jake E DelmoreConstantine S Mitsiades
Sep 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jennifer A MertzRobert J Sims
Nov 9, 2011·Nature Medicine·Melinda Wenner Moyer
Jan 5, 2013·Current Topics in Developmental Biology·Binyamin D Berkovits, Debra J Wolgemuth
Feb 23, 2013·Cancer Discovery·Alexandre PuissantKimberly Stegmaier
Oct 9, 2013·The Journal of Experimental Medicine·Deanna A MeleJose M Lora
Nov 20, 2013·Molecular and Cellular Biology·Sebastian WienerroitherThomas Decker
Apr 9, 2015·Bioorganic & Medicinal Chemistry Letters·Michael C HewittBrian K Albrecht
May 21, 2015·Oncotarget·Marie-Magdelaine CoudéClaude Gardin
Nov 18, 2015·Journal of Medicinal Chemistry·Frank Anthony RomeroSteven Magnuson

❮ Previous
Next ❯

Citations

May 25, 2016·Journal of Medicinal Chemistry·Terry D CrawfordAndrea G Cochran
Sep 1, 2016·Cell Cycle·Sheela A Abraham, Tessa L Holyoake
Aug 25, 2016·Expert Opinion on Drug Discovery·Leonardo G FerreiraAdriano D Andricopulo
Sep 30, 2016·Journal of Medicinal Chemistry·Terry D CrawfordSteven Magnuson
Oct 23, 2016·Drug Discovery Today. Technologies·Dimitrios Spiliotopoulos, Amedeo Caflisch
Feb 15, 2017·Journal of Medicinal Chemistry·Zhiqing LiuJia Zhou
Mar 10, 2017·Expert Opinion on Drug Discovery·Veda PrachayasittikulChanin Nantasenamat
Mar 10, 2017·Expert Opinion on Drug Discovery·Holger GreschikThomas Günther
Jun 22, 2017·Journal of Chemical Information and Modeling·Jing XingMingyue Zheng
Nov 1, 2017·Organic & Biomolecular Chemistry·Hao JiangCheng Luo
Feb 23, 2018·Leukemia·K K JovanovićS Manier
Jun 13, 2018·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Yukihiro Itoh
Aug 8, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Stephani Joy Y MacalinoSun Choi
Mar 19, 2019·Journal of Enzyme Inhibition and Medicinal Chemistry·Zhimin ZhangZhengrong Shen
Jun 10, 2016·Nature·Sheela A AbrahamTessa L Holyoake
Nov 9, 2019·Physical Chemistry Chemical Physics : PCCP·Haiyang ZhongTingjun Hou
Jun 20, 2019·Current Drug Targets·Yingying ShiFujiang Guo
Dec 10, 2019·Expert Opinion on Therapeutic Patents·Tian LuCheng Luo
Aug 6, 2016·Cellular and Molecular Life Sciences : CMLS·Dequina A NicholasGerald V Denis
Sep 20, 2017·The Cancer Journal·Christopher B BentonKapil N Bhalla
Jul 18, 2017·Archiv der Pharmazie·Mostafa Radwan, Rabah Serya
Feb 6, 2017·Molecular Cancer·Tan Boon TohEdward Kai-Hua Chow
Dec 3, 2016·Epigenetics : Official Journal of the DNA Methylation Society·Montserrat Pérez-Salvia, Manel Esteller
Dec 14, 2018·MedChemComm·Yingchao DuanHongmin Liu
Feb 14, 2019·Journal of Computer-aided Molecular Design·Eva NittingerVickie Tsui
Nov 1, 2018·Current Medicinal Chemistry·Victoria Lucia AlonsoEsteban Serra
Feb 6, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Huihui ZhuJingji Jin
Nov 10, 2020·Leukemia & Lymphoma·Natalie Cheng ChenNaveen Pemmaraju
Feb 24, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jonathan M CooperLu Q Le
Jan 13, 2021·Nature Communications·Anne-Louise LatifPeter D Adams
Dec 19, 2020·Signal Transduction and Targeted Therapy·Jenna L CarterYubin Ge

❮ Previous
Next ❯

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Sarah PicaudPanagis Filippakopoulos
Cold Spring Harbor Symposia on Quantitative Biology
F W AltP Nisen
Nature Reviews. Drug Discovery
Panagis Filippakopoulos, Stefan Knapp
© 2021 Meta ULC. All rights reserved