Northwestern University

Jindan Yu

Gary E Schiltz

Disclosed are covalent inhibitors of enhancer zeste homolog 2 (EZH2) which may be utilized as EZH2 targeting agents. The disclosed compounds may be characterized as substituted 3-amino-5-phenylbenzamide compounds. The disclosed compounds may be utilized as covalent inhibitors of EZH2 and further may be derivatized to form proteolysis-targeting chimeric molecules (PROTACs) that target EZH2 for degradation. The disclosed compounds and PROTACs may be used in pharmaceutical compositions and methods for treating cell proliferative disorders associated with EZH2 activity, such as cancer.

Substituted 3-amino-5-phenylbenzamide compounds as covalent inhibitors of enhancer zeste homolog 2 (EZH2) and proteolysis-targeting chimeric derivatives thereof (PROTACs) that induce degradation of EZH2

Disclosed are compounds that bind to embryonic ectoderm development (EED) protein and proteolysis-targeting chimeric (PROTAC) derivatives thereof that induce degradation of EED. The disclosed compounds may be characterized as substituted [1,2,4]triazolo[4,3-c]pyrimidin-5-amine compounds. The disclosed PROTAC derivatives thereof typically include a first targeting moiety that binds to EED (M) which may be derived from the disclosed [1,2,4]triazolo[4,3-]pyrimidin-5-amine compounds that bind to EED. The first targeting moiety typically is linked via a bond or a linker (L) to a second targeting moiety that binds to an E3 ubiquitin ligase (M). As such, the disclosed PROTACS may be described as having a formula M-L-Mor M-L-M, wherein Mhas a formula of where R, n, and x are as described herein.

Substituted [1,2,4]triazolo[4,3-c]pyrimidin-5-amines and proteolysis-targeting chimeric derivatives thereof (PROTACs) that induce degradation of embryonic ectoderm development (EED) protein

Disclosed are substituted pyrrolidones and piperidones which may be utilized as EZH2 targeting agents. The substituted pyrrolidones and piperidones may include substituted 2-pyrrolidones and 2-piperidones. The disclosed pyrrolidones and piperidones may be used in pharmaceutical compositions and methods for treating cell proliferative disorders such as cancer.

Growing community of inventors

Evanston, IL, United States of America

Jindan Yu