NOVEL BROMODOMAIN (BRD4) SMALL MOLECULE INHIBITORS FOR TARGETED TREATMENT OF CANCER
April 25, 2014Bromodomain-containing proteins function as chromatin modifiers and mediators of protein-protein interactions, controlling gene expression. 
BRDs have been functionally implicated in numerous disease processes, including cancer, and small molecule inhibitors have been developed with some advancing to early clinical trials in cancer. BRD4 is a member of the BET (Bromodomain and extra terminal domain) family proteins containing two tandem bromodomains and is the target of drug discovery efforts by Mount Sinai researchers who have developed novel composition of matter inhibitors of BRD4.
Current Development Status
- Significant in vitro studies completed
- Mouse xenografts of Triple Negative Breast Cancer demonstrate tool compound capability to shrink tumors
- Compounds with drug like properties available for further development
Applications
- Oncology
Advantages
- Structure guided generation of compounds
- Series of compounds with low nanomolar affinity
- Superior binding and reduction of tumor burden in head-to-head comparisons of other commercially available bromodomain inhibitors
- Differential selectivity between the two bromodomains in BRD4 (growing evidence suggests each has a different biological function and one may be more desirable to target)
Publications
- Shi, J, “Disrupting the Interaction of BRD4 with Diacetylated Twist Suppresses Tumorigeneis in Basal-like Breast Cancer,” Cancer Cell, 25, 210-225
Patent Status
- International Application No. PCT/US2012/026308 filed February 23, 2012
- Status: Published. International Publication No. WO 2012/116170
- Chinese Application 2012280019964 filed February 23, 2012
- Status: Published. CN Publication No. CN103547152
- US Utility Application 14/001,074 filed August 23, 2013
- Status: Published. US Publication No. US-2014-0066410-A1
- Foreign Pending Applications: AU, CA, EP filed February 23, 2012
Contact Information
Jeanne Farrell, PhD
Business Development Director
Mount Sinai Innovation Partners | Icahn School of Medicine at Mount Sinai
Phone: 646.605.7314