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

The Rockefeller University

Beth Israel Deaconess Medical Center, Inc.

Icahn School of Medicine at Mount Sinai

University of Utah Research Foundation

The Brigham and Women's Hospital, Inc.

The University of North Carolina at Chapel Hill

Duke University

Dana-farber-cancer Institute Inc.

Whitehead Institute for Biomedical Research

Min Shen

Matthew Brian Boxer

Li Liu

Anton Simeonov

Mindy Irene Emily Davis

Rajan Pragani

Craig J Thomas

Kun Ping Lu

Wenwei Huang

Barry S Coller

Xiao Zhen Zhou

Martin J Walsh

Douglas S Auld

Kyle Ryan Brimacombe

Shuo Wei

Jason Matthew Rohde

Marta Filizola

Joshua McCoy

Gregory D Cuny

Xiaodong Wang

Ajit Jadhav

Arthur Lee

Asaf Alimardanov

Paul B Yu

Andrew Louis McIver

John C McKew

Agustin H Mohedas

Kent Lai

Manshu Tang

Cordelle D Tanega

Xin Xu

Gurmit Singh Grewal

Surendra Karavadhi

David Sabatini

Matthew E Hall

Daniel Jason Urban

Jian-kang Jiang

Joseph Rittiner

Nicole Calakos

Zachary F Caffall

Ganesha Rai Bantukallu

Natalia Martinez

Michael Pacold

Wei Zhao

Jennifer T Fox

Zhuyin Li

Yuhong Fang

Andrew Louis Mciver

Mindy Irene Davis

Matthew Hall

Anton Momtchilov Simeonov

The present disclosure provides methods and compositions for the treatment, identification, diagnosis, and prognosis of dystonia, or dystonia related disorders.

Compositions and methods for identifying and treating dystonia disorders

The present invention provides compounds of Formula (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, pro-drugs, and compositions thereof. Also provided are methods and kits involving the compounds of Formula (I), (II) or (III) for treating diseases associated with the over-expression of phosphoglycerate dehydrogenase (PHGDH) in a subject, such as proliferative diseases (e.g., cancers (e.g., breast cancer, ER negative breast cancer, melanoma, cervical cancer), benign neoplasms, diseases associated with angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases). Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the activity of PHGDH or inhibit the serine biosynthetic pathway, or both.

Inhibitors of phosphoglycerate dehydrogenase (PHGDH) and uses thereof

The invention features compositions and methods for inhibiting the Pin1 protein, and the treatment of disorders characterized by elevated Pin1 levels.

Methods and compositions for the inhibition of PIN1

A compound of Formula II or a pharmaceutically acceptable salt thereof, wherein CyN is a cyclic amine group bound via a nitrogen atom; X is C or N; Rand Rare each independently a halogen, CN, CF, CHF, CHF, a C-C10alkyl group, a C1-Calkoxy group, a di(C-Calkyl)amino; m and n are each independently 1, 2, or 3, and represents either a single bond or a double bond, wherein the racemic mixture of 3-(4-(4-chlorophenyl)thiazol-2-yl)-1-(2-ethyl-5-methoxyphenyl)-6-(2-methylprop-1-en-1-yl)-5-(piperazine-1-carbonyl)pyridin-2(1H)-one atropisomers is excluded.

Thiazole derivatives useful as mutant IDH1 inhibitors for treating cancer

Compounds of Formula I and Formula II and the pharmaceutically acceptable salts thereof are disclosed The variables A, B, Y, Z, X, X, Rand Rare disclosed herein. The compounds are useful for treating cancer disorders, especially those involving mutant IDH1 enzymes. Pharmaceutical compositions containing compounds of Formula I or Formula II and methods of treatment comprising administering compounds of Formula I and Formula II are also disclosed. 

Mutant IDH1 inhibitors useful for treating cancer

Disclosed are inhibitors of human galactokinase of formula (I) that are useful in treating or preventing a galactokinase mediated disease or disorder, e.g., galactosemia. Also disclosed are a composition comprising a pharmaceutically acceptable carrier and at least one inhibitor of the invention, and a method of treating or preventing such disease or disorder in a mammal. Formula (I). 

Galactokinase inhibitors for the treatment and prevention of associated diseases and disorders

Methods and compositions for the inhibition of Pin1

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

Disclosed are pyruvate kinase M2 activators which are compounds of Formula (I), including those of Formula (II), wherein A, A, L, R, Rto R, Xto X, k, n, and m are as defined herein, that are useful in treating a number of diseases that are treatable by the activation of PKM2, for example, cancer. A-NR-L-A(I). 

Activators of human pyruvate kinase

The present invention relates to compounds of Formula P-I where the variables (e.g. R, Y, A, R, R, R, R, R, R, R, R, R, R, or R) and compositions useful for inhibiting and/or reducing platelet deposition, adhesion and/or aggregation. The present invention further relates to methods for the treatment or prophylaxis of thrombotic disorders, including stroke, myocardial infarction, unstable angina, peripheral vascular disease, abrupt closure following angioplasty or stent placement and thrombosis as a result of vascular surgery.

Oxadiazolo[3,2-A]pyrimidines and thiadiazolo[3,2-A]pyrimidines

Disclosed are inhibitors of human galactokinase of formula (1) that are useful in treating or preventing a galactokinase mediated disease or disorder, e.g., galactosemia. Also disclosed are a composition comprising a pharmaceutically acceptable carrier and at least one inhibitor of the invention, and a method of treating or preventing such disease or disorder in a mammal. Formula (I). 

The present invention relates to compounds and compositions of Formula P useful for inhibiting and/or reducing platelet deposition, adhesion and/or aggregation. The definitions of variables A, B, R, R, R, R, R', R, R&#x2032;, R, R, R&#x2032;, R, and R&#x2032; are provided in the disclosure. The present invention further relates to methods for the treatment or prophylaxis of thrombotic disorders, including stroke, myocardial infarction, unstable angina, peripheral vascular disease, abrupt closure following angioplasty or stent placement and thrombosis as a result of vascular surgery.

7-(piperazin-1-yl)-5H-[1,3,4]thiadiazolo[3,2-A]pyrimidin-5-ones for the treatment of thrombotic disorders

The present invention relates to compounds of formula P-1 and related compounds and compositions useful for inhibiting and/or reducing platelet deposition, adhesion and/or aggregation. The definitions of A, Y, R, R, R, R, R, R, R, R, R, R, R, and Rare provided herein. The present invention further relates to methods for the treatment or prophylaxis of thrombotic disorders, including stroke, myocardial infarction, unstable angina, peripheral vascular disease, abrupt closure following angioplasty or stent placement and thrombosis as a result of vascular surgery. 

Oxadiazolo[3,2-a]pyrimidines and thiadiazolo[3,2-a]pyrimidines

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Boyds, MD, United States of America

Min Shen