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

Vanderbilt University

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

University of Pennsylvania

The University of Texas System

University of California

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

Leonard M Neckers

Alex Gregory Waterson

Daniel Jason Urban

Victor M Darley-Usmar

Anton Simeonov

William J Moore

David Joseph Maloney

Ajit Jadhav

Gary Allen Sulikowski

Kwangho Kim

Xin Hu

Plamen P Christov

Shyh Ming Yang

Kyle Ryan Brimacombe

Somnath Jana

Bryan T Mott

Chi V Dang

Jane B Neckers

Jennifer L Kouznetsova

Ganesh Rai Bantukallu

Matthew E Hall

Marc Cox

Yeong Sang Kim

Aki Iwai

Yangmin Ning

Heather A Balsiger

John A Beutler

W Marston Linehan

Robert J Fletterick

Ross P Holmes

Kyle David Wood

John Knight

Johanny Kugelman-Tonos

Min-Jung Lee

Bradley T Scroggins

David J Maloney

Jane B Trepel

Ganesha Rai Bantukallu

Sunmin Lee

Carole Ac Sourbier

Johanny Tonos De Leon

Lyn D Olson

Daniel A Geselowitz

Carole Sourbier

Marc B Cox

Johanny Meneses De Leon

Plamen Christov

Matthew Hall

Brian T Mott

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 methods of treating a patient having primary hyperoxaluria or idiopathic hyperoxaluria comprising administering a therapeutically effective amount of compound of the formula and pharmaceutically acceptable salts, solvates, and hydrates thereof to the patient. The variables, e.g. ring A, n, R, R, R, X, Y, and Z are defined herein. These compounds act as lactate dehydrogenase inhibitors and are useful inhibiting the conversion of glyoxylate to oxalate. When administered to a patient having a disease or disorder associated with elevated oxalate levels, such as PH type 1, type 2, or type 3 or idiopathic hyperoxaluria the compounds prevent or substantially reduce the amount and buildup of oxalate the patient's kidneys, bladder, urinary tract and other parts of the patient's body.

Treating primary or idiopathic hyperoxaluria with small molecule inhibitors of lactate dehydrogenase

The disclosure provides methods of treating a patient having primary hyperoxaluria or idiopathic hyperoxaluria comprising administering a therapeutically effective amound of compound of the formula and pharmaceutically acceptable salts, solvates, and hydrates thereof to the patient. The variables, e.g. ring A, n, R, R, R, X, Y, and Z are defined herein. These compounds act as lactate dehydrogenase inhibitors and are useful inhibiting the conversion of glyoxylate to oxalate. When administered to a patient having a disease or disorder associated with elevated oxalate levels, such as PH type 1, type 2, or type 3 or idiopathic hyperoxaluria the compounds prevent or substantially reduce the amount and buildup of oxalate the patient's kidneys, bladder, urinary tract and other parts of the patient's body.

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 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

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. 

Pharmaceutical compositions that bind to a predicted FK506 Binding Protein 52 (FKBP52) interaction surface on the androgen receptor hormone binding domain, otherwise known as FKBP52 Targeting Agents (FTAs) are provided. These compositions of the present invention are found to specifically recognize the FKBP52 regulatory surface on the androgen receptor and inhibit FKBP52 from functionally interacting with the androgen receptor. Compositions comprising the pharmaceutical composition, as well as methods of use, treatment and screening are also provided.

Pharmaceutical compositions which inhibit FKBP52-mediated regulation of androgen receptor function and methods of using same

Disclosed is a method of activating protein kinase C theta (PKC&#x3b8;) in an HIV or HTLV infected animal comprising administering to the animal an effective amount of a compound of formula (I): Formula (I), or an epimer thereof; wherein Ar and R-Rare described herein. Examples of diseases or conditions associated with PKC&#x3b8; include HIV1 infection, AIDS, HTLV infection, and adult T cell leukemia/lymphoma. 

Methods of treating patients infected with HIV and HTLV

Disclosed are methods of treating an animal for insulin resistance and associated diseases or conditions, activating the transcriptional activity of heat shock factor 1 (HSF1), or inducing the expression of heat shock protein 70 (HSP70) in an animal in need thereof, wherein the methods involve administering an effective amount of one or more compounds of formula (I) or an epimer thereof, wherein Ar, and R-Rare described herein. Examples of diseases or conditions associated with insulin resistance include diabetes, obesity, inflammation, metabolic syndrome, polycystic ovary disease, arteriosclerosis, non-alcoholic fatty liver disease, reproductive abnormality in a female, and growth abnormality. 

Methods of treating or preventing insulin resistance and associated diseases and conditions

A method for detecting mycoplasma infection in a sample by contacting the sample with labeled oligonucleotides, then measuring incorporation (if any) of the label into mycoplasma RNA.

Method for detection of mycoplasma

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Bethesda, MD, United States of America

Leonard M Neckers