Northwestern University

Decode Genetics Ehf

Gary E Schiltz

Rama K Mishra

Jindan Yu

Karl A Scheidt

Atul D Jain

Sarki A Abdulkadir

Huiying Han

Javier Izquierdo-Ferrer

Ali Shilatifard

Edwin Richard Smith

Kaiwei Liang

Derek A Wainwright

Leonidas C Platanias

Matthew R Clutter

Mark E Gurney

Timothy J Hagen

Vincent Premaratna Sandanayaka

Jasbir Singh

Georgeta Hategan

Richard J Miller

Alexander Kiselyov

Teepu Siddique

Steven T Rosen

Alex Burgin

Thomas J Lukas

Yong Wan

Junlong Chi

Zhuan Zhou

Nancy L Krett

Chisu Song

Richard T D'Aquila

Meejeon Roh

Hasan Arrat

Adalie Motta

Kristen Stoltz

Ada J Kwong

Purav Vagadia

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 having the Formula I: where Ris as disclosed herein. The disclosed PROTAC derivatives thereof typically include a first targeting moiety that binds to BED (M) which may be derived from the disclosed [1,2,4]triazolo[4,3-c]pyrimidin-5-amine compounds having the Formula I 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.

Substituted [1,2,4]triazolo[4,3-c]pyrimidines that induce degradation of embryonic ectoderm development (EED) protein

Described herein are compounds of Formula I, or their pharmaceutically acceptable salts thereof, compositions comprising the same, and methods of using such compounds or compositions in inducing Cdc20 degradation in a cell, blocking mitotic progression, inhibiting tumor proliferation, treating cancer, and/or re-sensitizing a subject to cancer treatment with tamoxifen.

Bifunctional compounds comprising Apcin-A and their use in the treatment of cancer

Disclosed are proteolysis-targeting chimeric molecules (PROTACs) that induce degradation of IDO protein. The disclosed PROTACs typically include a first targeting moiety that binds to IDO (Miro). 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.

Proteolysis-targeting chimeric molecules (PROTACs) that induce degradation of indoleamine 2,3-dioxygenase (IDO) protein

Disclosed are compounds, pharmaceutical compositions, and methods of treatment. The disclosed compounds are based on fused 1,4-diazepine and pyrrolidinedione scaffolds. The compounds may be utilized in pharmaceutical compositions and methods for treating diseases and disorders associated with cell proliferation such as cancer and may have a formula illustrated as follows:

Substituted fused pyrrolo-diazepinones and uses thereof

Disclosed are substituted heterocycle compounds including substituted pyrazoles, substituted pyrimidines, and substitute triazoles. The substituted heterocycles disclosed herein are shown to be useful in inhibiting c-MYC and may be utilized as therapeutics for treating cancer and cell proliferative disorders.

Substituted heterocycles as c-MYC targeting agents

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.

Substituted pyrrolidones and piperidones as small molecule inhibitors of EZH2 and EED protein binding

Disclosed are proteolysis-targeting chimeric molecules (PROTACs) that induce degradation of c-MYC protein. The disclosed PROTACs typically include a first targeting moiety that binds to c-MYC (M) which may be derived from a substituted heterocycle that binds to c-MYC such as a substituted pyrazole. 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.

Proteolysis-targeting chimeric molecules (PROTACs) that induce degradation of c-MYC protein

Disclosed are proteolysis-targeting chimeric molecules (PROTACs) that induce degradation of IDO protein. The disclosed PROTACs typically include a first targeting moiety that binds to IDO (M). 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.

Disclosed are compounds which may be utilized to inhibit transcription by RNA Polymerase II (Pol II), and in particular to disrupt the Super Elongation Complex (SEC). The compounds may be utilized in pharmaceutical compositions and methods for treating diseases and disorders associated with the biological activity of SEC, and in particular, diseases and disorders that are associated with high levels of expression of genes whose expression is SEC-dependent and that promote, support, or otherwise are required for the disease or disorder such as cancers.

Small molecules for disrupting the super elongation complex and inhibiting transcription elongation for cancer therapy

Disclosed are indazole compounds and derivatives thereof for use as modulators of the activity of mitogen-activated protein kinase 4 (MEK4). The disclosed compounds include 3-Arylindazoles which may be formulated in pharmaceutical composition for treating cell proliferative diseases and disorders associated with MEK4 activity, including cancer.

3-arylindazoles as selective MEK4 inhibitors

Disclosed are compounds, pharmaceutical compositions, and methods of treatment. The disclosed compounds are based on fused 1,4-diazepine and pyrrolidinedione scaffolds. The compounds may be utilized in pharmaceutical compositions and methods for treating diseases and disorders associated with cell proliferation such as cancer and may have a formula illustrated as follows: 

Growing community of inventors

Naperville, IL, United States of America

Gary E Schiltz