Albert Einstein College of Medicine

Louisiana State University and Agricultural & Mechanical College

University of Kansas

Icahn School of Medicine at Mount Sinai

The State University of New York

The United States Government As Represented by the Department of Veterans Affairs

Das, Bhaskar C.

Bhaskar C Das

Evripidis Gavathiotis

Nikhil V Dhurandhar

Ana Maria Cuervo

Qisheng Xin

Darren Paul Wallace

Sandeep Mallipattu

Sridhar Mani

Ganjam V Kalpana

John Cijiang He

Zhengzhe Li

Kyung Lee

Paul Jubinsky

Ruijie Liu

Mary K Short

Wenzhen Xiao

The present disclosure is concerned with small molecule modulators of KLF15 signaling useful for treating various disorders such as, for example, kidney disease (e.g., chronic kidney disease), heart disease, obesity, or a neurodegenerative disorder (e.g., amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease, spinal muscular atrophy, traumatic brain injury, vascular dementia, Huntington's disease, mental retardation, and attention deficit and hyperactivity disorder (ADHD)). This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Krüppel-like factor 15 (KLF15) small molecule agonists in kidney disease

Kr&#xfc;ppel-like factor 15 (KLF15) small molecule agonists in kidney disease

Compounds, compositions and methods are provided for selectively activating chaperone-mediated autophagy (CMA), protecting cells from oxidative stress, proteotoxicity and lipotoxicity, and/or antagonizing activity of retinoic acid receptor alpha (RAR&#x3b1;) in subjects in need thereof.

Retinoic acid receptor antagonists as chaperone-mediated autophagy modulators and uses thereof

Compounds that are selective inhibitors of Smad3 activation are disclosed. The compounds have the following structure: in which Z is an oxadiazole. The compounds disclosed are useful in treatment of fibrotic disease, particularly renal fibrosis, and similar diseases associated with the dysregulation of the HIPK2/Smad3 signaling pathway.

Oxadiazole inhibitors of HIPK2 for treating kidney fibrosis

Compounds can be used for treating polycystic kidney disease (PKD). As such, these compounds can be used in associated methods. The methods can include: method of modulating (e.g., activating) Liver kinase B1 (LKB1); method of modulating (e.g., decreasing activity) mammalian target of rapamycin (mTOR). The methods may include introducing the compound in a therapeutically effective amount to a subject having PKD. The methods may include introducing the compound in a therapeutically effective amount to a subject having Autosomal Dominant PKD. The compounds can be used in methods of treating a disease modulated by a mTOR pathway, which can include introducing the compound in a therapeutically effective amount to a subject having the disease modulated by the mTOR pathway. The disease modulated by mTOR is selected from the group consisting of multiple types of cancer, including breast cancer, renal cell carcinoma, colorectal cancer, prostate cancer, non-small cell lung cancer, cervical cancer, ovarian cancer, skin cancer, glioblastoma, bone metastatic cancer, head and neck cancer, and leukemia, kidney disease, obesity, neuro disorders and alcohol-related chronic diseases.

LKB1-AMPK activators for therapeutic use in polycystic kidney disease

Compounds are provided for use in treating polycystic kidney disease (PKD) and in associated methods that include a method of modulating (e.g., activating) Liver kinase B1 (LKBI); and a method of modulating (e.g., decreasing activity) mammalian target of rapamycin (mTOR). The methods may include introducing the compound in a therapeutically effective amount to a subject having PKD. The methods may include introducing the compound in a therapeutically effective amount to a subject having Autosomal Dominant PKD. The compounds can be used in methods of treating a disease modulated by a mTOR pathway, which can include introducing the compound in a therapeutically effective amount to a subject having the disease modulated by the mTOR pathway. The disease modulated by mTOR is selected from the group consisting of multiple types of cancer, leukemia, kidney disease, obesity, neuro disorders and alcohol-related chronic diseases.

The invention relates to amino nitrile compounds. Such compounds can increase glucose uptake by cells and preferably do not substantially increase adipogenesis.

Small molecule analogs of E4orf1

A compound includes the structure of general Formula II, pharmaceutically acceptable salts thereof, and/or solvates thereof: wherein R, R, R, are independently selected from the group consisting of null, hydroxy, alkoxy, and halo, or Rand Rtaken together form a cyclic boronate ester and Ris null; wherein when four bonds to boron are present, boron bears a formal negative charge and the structure further comprises a countercation that is potassium or sodium, X, X, X, and Xare independently selected from the group consisting of O, CH, and N, with the proviso that no more than two of combined O and N are selected, and Z is selected from the group consisting of hydrogen, alkyl, aryl, heteroaryl, and halogen, any of which may be optionally substituted. Such compounds can increase glucose uptake by cells and preferably do not substantially increase adipogenesis.

Compositions and methods for improving glucose uptake

A method of treating a disease comprising administering to a subject a therapeutically effective amount of a compound that includes the structure of general Formula II, pharmaceutically acceptable salts thereof, and/or solvates thereof: wherein R, R, R, are independently selected from the group consisting of null, hydroxy, alkoxy, and halo, or Rand Rtaken together form a cyclic boronate ester and Ris null; wherein when four bonds to boron are present, boron bears a formal negative charge and the structure further comprises a countercation that is potassium or sodium, X, X, X, and Xare independently selected from the group consisting of O, CH, and N, with the proviso that no more than two of combined O and N are selected, and Z is selected from the group consisting of hydrogen, alkyl, aryl, heteroaryl, and halogen, any of which may be optionally substituted. Such compounds can increase glucose uptake by cells and preferably do not substantially increase adipogenesis.

A compound includes the structure of general Formula (II), pharmaceutically acceptable salts thereof, and/or solvates thereof: wherein R, R, R, are independently selected from the group consisting of null, hydroxy, alkoxy, and halo, or Rand Rtaken together form a cyclic boronate ester and Ris null; wherein when four bonds to boron are present, boron bears a formal negative charge and the structure further comprises a countercation that is potassium or sodium, X, X, X, and Xare independently selected from the group consisting of O, CH, and N, with the proviso that no more than two of combined O and N are selected, and Z is selected from the group consisting of hydrogen, alkyl, aryl, heteroaryl, and halogen, any of which may be optionally substituted. Such compounds can increase glucose uptake by cells and preferably do not substantially increase adipogenesis.

The application discloses ketoconazole derivatives that are antagonists of the human pregnane X receptor (PXR), methods of preparing the derivatives, uses of the derivatives with drug therapy, and methods of inhibiting tumor cell proliferation and multidrug resistance using inhibitors of PXR.

Ketoconazole-derivative antagonist of human pregnane X receptor and uses thereof

The present invention relates to inhibitors of mitochondria-associated, granulocyte-macrophage colony stimulating factor signaling molecule (Magmas), and related compositions and uses thereof.

Growing community of inventors

West Nyack, NY, United States of America

Bhaskar C Das