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

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

  • J Med Chem. 2016 Feb 25;59(4):1330-9. doi: 10.1021/acs.jmedchem.5b01882.
Brian K Albrecht 1,  Victor S Gehling 1,  Michael C Hewitt 1,  Rishi G Vaswani 1,  Alexandre Côté 1,  Yves Leblanc 1,  Christopher G Nasveschuk 1,  Steve Bellon 1,  Louise Bergeron 1,  Robert Campbell 1,  Nico Cantone 1,  Michael R Cooper 1,  Richard T Cummings 1,  Hariharan Jayaram 1,  Shivangi Joshi 1,  Jennifer A Mertz 1,  Adrianne Neiss 1,  Emmanuel Normant 1,  Michael O'Meara 1,  Eneida Pardo 1,  Florence Poy 1,  Peter Sandy 1,  Jeffrey Supko 1,  Robert J Sims 3rd 1,  Jean-Christophe Harmange 1,  Alexander M Taylor 1,  James E Audia 1
Affiliations

Affiliation

  • 1 Constellation Pharmaceuticals , 215 First Street, Suite 200, Cambridge, Massachusetts 02142, United States.
PMID: 26815195 DOI: 10.1021/acs.jmedchem.5b01882
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).

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