The Brigham and Women's Hospital, Inc.

Harvard College

Tufts University

Minnesota Mining and Manufacturing Company

The General Hospital Corporation

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Dana-farber-cancer Institute Inc.

3m Innovative Properties Company

University of Georgia Research Foundation Inc

Boston University

Chinese Academy of Sciences

Duke University

The Ohio State University

Indiana University

University of Massachusetts

Gregory D Cuny

James R Hauske

Liming Shao

Brian M Aquila

Marcie A Glicksman

Thomas D Bannister

Alexei Degterev

Xinhe Wu

Heike S Radeke

Junying Yuan

Fengjiang Wang

Michael Z Hoemann

Michele L R Heffernan

Roger L Xie

Lixin Qiao

Paul E Persons

Joanne M Holland

Ross L Stein

Albert Edge

Stanley C Busman

Paul B Yu

Sang-Jun Jeon

Kathleen Seyb

Prakash Jagtap

Richard F Rossi

Richard J Ellis

Jun Xian

Arthur Lee

Krzysztof Antoni Zaklika

Donald L Heefner

Donald W Kessler

Lizbeth K Hedstrom

John C McKew

Xin Teng

Agustin H Mohedas

Anita Melikian-Badalian

Gnanasambandam Kumaravel

Mandapati Kavitha

Min Huang

Terrance P Smith

Kevin D Landgrebe

William Donald Ramsden

Alan D D'Andrea

Asaf Alimardanov

Min Shen

John A Porco, Jr

Kenneth D Bloch

Tran V Thien

Kevin J Hodgetts

Douglas Raines

Charles C Hong

Randall T Peterson

Syed Shaukat Husain

Joseph F Cotten

Stuart A Forman

Keith W Miller

Jeanne E Haubrich

Deviprasad R Gollapalli

April Case

David Wilson

Sameer Nikhar

Michelle L R Heffernan

Jingrong Cao

Gurmit Singh Grewal

Boris Striepen

Suresh K Gorla

Steven L Mathieu

Xin Xu

Yukari Y Perrella

David Cohen

Vincent Darmency

Neil Wagle

Hrvoje Lusic

Ekaterina Y Shishova

Wei Ping Zheng

Elliot J Androphy

Kai W Wucherpfennig

Ashok Sengupta

Charles E Shelburne

Frank A Brandys

David John Hastings

Philip Edward Sanderson

Xiuli Huang

Chien-Liang Glenn Lin

Donald C Lo

Paresma R Patel

Li-An Yeh

Jonathan Cherry

Suresh Kumar Gorla

Thomas Gainer

Sungwoon Choi

Junichi Hitomi

Melissa Call

Chandrika D Mudalige

Sivapriya Kirubakaran

Ian Chopra

Sushil K Maurya

Corey R Johnson

Jihan Khan

Xeuchao Xing

Identified compounds demonstrate protein kinase inhibitory activity. More specifically, the compounds are demonstrated to inhibit receptor interacting kinase 2 (RIPK2) and/or Activin-like kinase 2 (ALK2). Compounds that are either dual RIPK2/ALK2 inhibitors or that preferentially inhibit RIPK2 or ALK2 could provide therapeutic benefit.

Pyrido[2,3-d]pyrimidin-7-ones and related compounds as inhibitors of protein kinases

Identified compounds demonstrate protein kinase inhibitory activity. More specifically, the compounds having the structures below (I) are demonstrated to inhibit receptor interacting kinase 2 (RIPK2) and/or Activin-like kinase 2 (ALK2). Compounds that are either dual RIPK2/ALK2 inhibitors or that preferentially inhibit RIPK2 or ALK2 could provide therapeutic benefit. 

This invention generally provides compounds, pharmaceutical compositions, and methods for their use, which include methods that result in increased expression in an Atoh1 gene (e.g., Hath1) in a biological cell. More specifically, the invention relates to the treatment of diseases and/or disorders that would benefit from increased Atoh1 expression, e.g., a hearing impairment or imbalance disorder associated with a loss of auditory hair cells, or a disorder associated with abnormal cellular proliferation.

Compounds that enhance Atoh1 expression

Identified compounds demonstrate protein kinase inhibitory activity and inhibition of dependent cell signaling pathways, such as NOD2 cell signaling. More specifically, the compounds are demonstrated to inhibit receptor interacting kinase 2 (RIPK2) and/or Activin-like kinase 2 (ALK2). Compounds that are either dual RIPK2/ALK2 inhibitors or that preferentially inhibit RIPK2 or ALK2 could provide therapeutic benefit.

Compositions and methods for inhibiting protein kinases

The present invention relates to 2-amino-4-arylpyrimidine and 2-amino-4-aryltriazine compounds as inhibitors of heat shock protein 90 family of chaperone proteins. The invention also features pharmaceutical compositions and kits that include the compounds and compositions of the invention. The invention further relates to the medical use of these compounds and compositions for the treatment of a disorder in a subject. For example, the disorder is a neurodegenerative disease.

Pyrimidine compounds and methods using the same

Provided are small molecule inhibitors of ubiquitin specific protease 1 (USP1) activity and methods for their use in treating and characterizing cancers. The small molecule USP1 inhibitors of the invention are particularly useful in the treatment of cancers that are resistant to DNA cross-linking agents.

Small molecule inhibitors of USP1 deubiquitinating enzyme activity

The present invention provides bicyclic heteroaryl inhibitors of BMP signaling and compositions and methods for inhibiting BMP signaling. Exemplary compounds include those of Formula I:  These compounds and compositions may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation. These compounds and compositions may also be used to reduce circulating levels of ApoB-100 or LDL and treat or prevent acquired or congenital hypercholesterolemia or hyperlipoproteinemia; diseases, disorders, or syndromes associated with defects in lipid absorption or metabolism; or diseases, disorders, or syndromes caused by hyperlipidemia.

Compositions and methods for inhibiting BMP

Described herein are compounds, and pharmaceutically acceptable salts and prodrugs thereof, which are useful as inhibitors of IMPDH. In certain embodiments, a compound of the invention selectively inhibits a parasitic IMPDH versus a host IMPDH. Further, the invention provides pharmaceutical compositions comprising one or more compounds of the invention. The invention also relates to methods of treating various parasitic and bacterial infections in mammals. Moreover, the compounds may be used alone or in combination with other therapeutic or prophylactic agents, such as anti-virals, anti-inflammatory agents, antimicrobials and immunosuppressants.

Compounds and methods for treating mammalian gastrointestinal microbial infections

The present invention provides small molecule inhibitors of BMP signaling. These compounds may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation. These compounds may also be used to reduce circulating levels of ApoB-100 or LDL and treat or prevent acquired or congenital hypercholesterolemia or hyperlipoproteinemia; diseases, disorders, or syndromes associated with defects in lipid absorption or metabolism; or diseases, disorders, or syndromes caused by hyperlipidemia.

BMP inhibitors and methods of use thereof

The present invention relates to heterocyclic compounds (e.g., compounds described by Formula (I)) and pharmaceutically acceptable salts thereof. The invention also features pharmaceutical compositions that include these compounds and their use in therapy for treating conditions in which necroptosis is likely to play a substantial role. The heterocyclic compounds described herein can also achieve improved activity and selectivity towards RIP1 and/or RIP3. 

Substituted indoles and pyrroles as RIP kinase inhibitors

This invention relates to compounds of Formulas I, II, and III, and their use as inhibitors of phosphatidylcholine transfer protein (PC-TP). The invention further relates to pharmaceutical compositions and methods of treatment of disorders related to the inhibition of PC-TP using the compounds of Formulas I, II, and III. Such disorders include obesity and disorders associated with obesity.

Phosphatidylcholine transfer protein inhibitors

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Houston, TX, United States of America

Gregory D Cuny