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

University of Pennsylvania

Vanderbilt University

The UAB Research Foundation (The University of Alabama at Birmingham)

University of California

University System of Maryland

Thomas Jefferson University

Beth Israel Deaconess Medical Center, Inc.

Children's National Medical Center

Other

The University of North Carolina at Chapel Hill

The United States of America As Represented by the Department of Health

Yale University

University of Delaware

The General Hospital Corporation

Anton Simeonov

David Joseph Maloney

Ajit Jadhav

Shyh Ming Yang

Kyle Ryan Brimacombe

Diane K Luci

Daniel Jason Urban

Alex Gregory Waterson

William J Moore

Gary Allen Sulikowski

Kwangho Kim

Leonard M Neckers

Xin Hu

Plamen P Christov

Victor M Darley-Usmar

Somnath Jana

Chi V Dang

Bryan T Mott

Min Shen

Matthew Brian Boxer

Rajan Pragani

Ganesh Rai Bantukallu

Jennifer L Kouznetsova

Mindy Irene Emily Davis

Adam Yasgar

Theodore Holman

Thomas S Dexheimer

Juan Jose Marugan

Kun Ping Lu

Marshall Lynn Summar

Xiao Zhen Zhou

David J Maloney

Peter Kofinas

David A Taylor-Fishwick

Michael Holinstat

Shuo Wei

Omar Bilal Ayyub

Juan Manuel Cabrera-Luque

Gary Cunningham

Adam Michael Behrens

Steven McKenzie

Nathan Patrick Coussens

Ganesha Rai Bantukallu

Samuel G Michael

William Chester Stafford

Jerry L Nadler

Natalia Martinez

Elias Set Jenö Arnér

Li Liu

Xiaodong Wang

Matthew E Hall

Andrew Louis McIver

Jason Matthew Rohde

Surendra Karavadhi

Diane Karen Luci

Elias Set Arner

Yu Liang

Thomas Kristie

Jodi Vogel

Zhihao Zhuang

Klaus Joachin Van Leyen

Qin Liang

Andrew S Rosenthal

Ganesha Rai

Wei Zhao

Yuhong Fang

Vasilis Vasiliou

Mindy Irene Davis

Omar Bilal Ayyup

Plamen Christov

Steven E Mckenzie

Theodore R Holman

Matthew Hall

Brian T Mott

Nathan Coussens

Klaus Van Leyen

Andrew Louis Mciver

Ty C Voss

Mark J Henderson

Bolormaa Baljinnyam

Provided is a compound of formula (I) in which Ar, R, U, V, W, X, and p are as described herein. Also provided are methods of using a compound of formula (I), including a method of treating cancer, a method of treating a patient with cancer cells resistant to an anti-cancer agent, and a method of inhibiting lactate dehydrogenase A (LDHA) and/or lactate dehydrogenase B (LDHB) activity in a cell.

Small molecule inhibitors of lactate dehydrogenase and methods of use thereof

The disclosure provides compounds of Formula I, which may be useful as aldehyde dehydrogenase inhibitors and the pharmaceutically acceptable salts thereof. The variables, J, R, G, Q, and ring A are defined herein. Aldehyde dehydrogenase inhibitors of Formula I are useful for treating a variety of conditions including cancer and inflammation. The disclosure includes methods for using compounds and salts of Formula I to treat colon cancer, pancreatic cancer, nasopharyngeal carcinoma, thyroid cancer, prostate cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, hepatocellular carcinoma, leukemia, brain tumors breast cancer, atherosclerosis, ischaemic heart disease, acne vulgaris, asthma, autoimmune diseases, autoinflammatory diseases, chronic prostatitis, glomerulonephritis, inflammatory bowel disease, pelvic inflammatory disease, reperfusion injury, rheumatoid arthritis, sarcoidosis, transplant rejection, vasculitis, and interstitial cystitis. The disclosure also includes pharmaceutical compositions containing a compound or salt of Formula I.

Substituted quinoline analogs as aldehyde dehydrogenase 1A1 (ALDH1A1) inhibitors

The disclosure provides compounds of Formula I, which may be useful as aldehyde dehydrogenase inhibitors and the pharmaceutically acceptable salts thereof. The variables, J, R, G, Q, and ring A are defined herein. Aldehyde dehydrogenase inhibitors of Formula I are useful for treating a variety of conditions including cancer and inflammation. The disclosure includes methods for using compounds and salts of Formula I to treat colon cancer, pancreatic cancer, nasopharyngeal carcinoma, thyroid cancer, prostate cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, hepatocellular carcinoma, leukemia, brain tumors breast cancer, atherosclerosis, ischaemic heart disease, acne vulgaris, asthma, autoimmune diseases, autoinflammatory diseases, chronic prostatitis, glomerulonephritis, inflammatory bowel disease, pelvic inflammatory disease, reperfusion injury, rheumatoid arthritis, sarcoidosis, transplant rejection, vasculitis, and interstitial cystitis. The disclosure also includes pharmaceutical compositions containing a compound or salt of Formula I. 

Human lipoxygenases (LOXs) are a family of iron-containing enzymes involved in catalyzing the oxidation of polyunsaturated fatty acids to provide the corresponding bioactive hydroxyeicosatetraenoic acid (HETE) metabolites. These eicosanoid signaling molecules are involved in a number of physiologic responses such as platelet aggregation, inflammation, and cell proliferation. Platelet-type 12-(S)-LOX (12-LOX) is of particular interest because of its demonstrated role in skin diseases, diabetes, platelet hemostasis, thrombosis, and cancer. Disclosed herein is the identification and medicinal chemistry optimization of a 4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide-based scaffold. The compounds display nM potency against 12-LOX and excellent selectivity over related lipoxygenases and cyclooxygenases. In addition to possessing favorable ADME properties, the compounds also inhibit PAR-4 induced aggregation and calcium mobilization in human platelets, and reduce 12-HETE in mouse/human beta cells. The compounds can also be used in methods for treating or preventing a 12-lipoxygenase mediated disease or disorder.

4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide derivatives as potent and selective inhibitors of 12-lipoxygenase

Provided is a compound of formula (I), in which Ar, R, U, V, W, X, and p are as described herein. Also provided are methods of using a compound of formula (I), including a method of treating cancer, a method of treating a patient with cancer cells resistant to an anti-cancer agent, and a method of inhibiting lactate dehydrogenase A (LDHA) and/or lactate dehydrogenase B (LDHB) activity in a cell.

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

There is provided compounds of formula (I) or pharmaceutically-acceptable salts thereof, wherein W, X, Y, Z, R, Rand Rhave meanings provided in the description, which compounds are useful in the treatment of cancers. 

Pyridazinones and their use in the treatment of cancer

The disclosure provides a compound of the formula (II) and pharmaceutically acceptable salts thereof. The variables, e.g. n, R, R, R, X, Y, and Z are defined herein. These compounds act as lactate dehydrogenase inhibitors and are useful for treating cancer and fibrosis. The compounds may be particularly useful for treating forms of cancer in which a metabolic switch from oxidative phosphorylation to glycolysis has occurred. The disclosure also provides pharmaceutical compositions containing a compound of this formula and method for treating patients having cancer, fibrosis, or other conditions in which a metabolic switch from oxidative phosphorylation to glycolysis has occurred. 

1 H-pyrazol-1-yl-thiazoles as inhibitors of lactate dehydrogenase and methods of use thereof

There is provided compounds of formula (I) or pharmaceutically-acceptable salts thereof, wherein L, R, R, R, Rand n have meanings provided in the description, which compounds are useful in the treatment of cancers. 

Pyridines and their use in the treatment of cancer

There is provided compounds of formula (I), or pharmaceutically-acceptable salts thereof, wherein X, Y, Z, Rand Rhave meanings provided in the description, which compounds are useful in the treatment of cancers. 

Tricyclic compounds and their use in the treatment of cancer

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

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Bethesda, MD, United States of America

Anton Simeonov