US Patent:
20200407371, Dec 31, 2020
Inventors:
- Boston MA, US
Lei Wu - Shanghai, CN
Kenneth C. Anderson - Wellesley MA, US
Yan Song - Brookline MA, US
Paul Park - Waltham MA, US
Dharminder Chauhan - Natick MA, US
Assignee:
DANA-FARBER CANCER INSTITUTE, INC. - Boston MA
International Classification:
C07D 495/14
A61P 35/00
Abstract:
Provided herein are bifunctional compounds that bind a target protein (e.g., a selected protein) and/or induce ubiquitination for degradation of the target protein. In particular, provided are compounds that bind a bromodomain or bromodomain-containing protein (e.g., BET proteins) or histone methyltransferases (HMTs, e.g., enhancer of zeste homolog 1 (EZH1), or FKBP12) and can promote its degradation by recruiting it to the ubiquitin receptor RPN13 (e.g., RA190), for proteasomal degradation. Also provided are pharmaceutical compositions comprising the bifunctional compounds, methods of treating and/or preventing diseases (e.g., proliferative diseases, cancers, benign neoplasms, pathological angiogenesis, inflammatory diseases, and autoimmune diseases) and musculoskeletal diseases, and methods of inducing the degradation of a target (e.g., a target protein) by recruiting it to the ubiquitin receptor RPN13 of the proteasome in a subject by administering a compound or composition described herein.
