Constellation Pharmaceuticals Presentation Highlights Enhanced EZH2 Target Engagement, Leading to Second-Generation EZH2 Inhibitor CPI-0209
- Category: Small Molecules
- Published on Wednesday, 12 June 2019 18:36
- Hits: 525
CAMBRIDGE, MA, USA I June 12, 2019 I Constellation Pharmaceuticals, Inc. (Nasdaq: CNST) today announced that Dr. Jacob Stuckey, Senior Scientist at Constellation Pharmaceuticals, gave an oral presentation titled Methods for Kinetic Assessment of High Affinity EZH2 Inhibitors: Identification of a 2nd Generation EZH2i with Improved Biological Activity and Extremely Long Residence Time at the Oxford Global Drug Discovery Summit in Berlin earlier today.
Dr. Stuckey described detailed studies conducted by Constellation Pharmaceuticals to characterize molecules from the Company’s second-generation EZH2 inhibitor program. As outlined in Dr. Stuckey’s presentation, potent EZH2 inhibitors present a number of unique challenges for measurement of biochemical potency and residence time. To meet these challenges, the Company developed customized biochemical and binding assays to evaluate these parameters. A key structural modification was identified that bestows prolonged residence time on multiple known EZH2-inhibitor scaffolds. Optimized second-generation EZH2 inhibitors display sub-pM potencies that translate into enhanced cell killing of EZH2-inhibitor-sensitive preclinical models both in vitro and in vivo.
The culmination of the Company’s second-generation EZH2 inhibitor program was the identification of CPI-0209, which reversibly binds to the PRC2 complex with sub-pM binding affinity and a residence time of >3 months. Constellation expects to file an Investigational New Drug (IND) application for CPI-0209 in June 2019.
About Constellation Pharmaceuticals
Constellation Pharmaceuticals is a clinical-stage biopharmaceutical company developing novel therapeutics that selectively modulate gene expression to address serious unmet medical needs in patients with cancer. The Company has a deep understanding of how epigenetic and chromatin modifications in cancer cells and in the tumor and immune microenvironment play a fundamental role in driving disease progression and drug resistance. Constellation is driving development of the EZH2 inhibitors CPI-1205 and CPI-0209 for the treatment of metastatic castration-resistant prostate cancer and other cancers as well as the BET inhibitor CPI-0610 for the treatment of myelofibrosis. The Company is also applying its broad research and development capabilities to explore other novel targets that directly and indirectly impact gene expression to fuel a sustainable pipeline of innovative small-molecule product candidates.
SOURCE: Constellation Pharmaceuticals