The Scripps Research Institute

Eolas Therapeutics, Inc.

Merck + Co., Inc.

University of Florida Research Foundation Inc

Astrazeneca Ab

Dana-Farber-Cancer Institute Inc.

Merck Sharp + Dohme Corp.

The Broad Institute, Inc.

The University of Toledo

Ember Therapeutics, Inc.

Theodore M Kamenecka

Yuanjun He

Patrick Griffin

Rong Jiang

Xinyi Song

William K Hagmann

Robert Jason Herr

Qin Jiang

Marcel Koenig

Steven Sigmund Wesolowski

Anne-Laure Blayo

Youseung Shin

William Nguyen

John Howard Hutchinson

Jean-Michel Andre Vernier

Steven P Govek

Matthew Surman

Roland W Bürli

Jörg Holenz

Stephen E DeLaszlo

Steven K Duddy

Derek R Duckett

Alice Asteian

Philip LoGrasso

Michael Darin Cameron

Beata Lecka-Czernik

Gavin Rumbaugh

Steve Young

Laszlo Radnai

Courtney Anne Miller

Sander G Mills

Malcolm MacCoss

Lihu Yang

Stuart L Schreiber

Jeffrey O Saunders

Alexander Pasternak

George A Doherty

Shrenik K Shah

Bruce M Spiegelman

Amy Ripka

Linus S Lin

Linda L Chang

Paul David Robbins

Richard A Mumford

Essa H Hu

Stephen D Goble

Celine Bonnefous

Partha Pratim Nag

Stephen E De Laszlo

Pere Puigserver

Laura J Niedernhofer

Clare E Gutteridge

Joshua A Bittker

Jonathan Z Long

Ginger Xu-Qiang Yang

Richard Pracitto

Roland Bürli

Brent R Lyda

Naresh Kumar

Thomas Burris

Hua Lin

Kfir Sharabi

Gabriela Mustata Wilson

Roger Schilling

Roland BÜRLI

The invention can provide compounds, analogs of blebbistatin, effective and selective inhibitors of nonmuscle myosin II relative to cardiac myosin II. Compounds can be used in the method of treating a disease, disorder, or medical condition in a patient, comprising modulating myosin II ATPase, such as treatment of substance abuse relapse disorder, or of renal disease, cancer and metastasis, benign prostate hyperplasia, hemostasis or thrombosis, nerve injury including retinal damage, lung fibrosis, liver fibrosis, arthrofibrosis, wound healing, spinal cord injury, periodontitis, glaucoma and immune-related diseases including multiple sclerosis; or wherein the disease, disorder, or medical condition comprises addiction including abuse of or addiction to anything classified as a Substance-Related or Addictive Disorder in the Diagnostic and Statistical Manual of Mental Disorders (DSM), such as, but not limited to, cocaine, opioids, amphetamines, ethanol,/marijuana, nicotine, and activities including gambling. Compounds are of general formula with substituents as defined herein.

Nonmuscle myosin ii inhibitors

The present application relates to certain halo-substituted piperidine compounds, pharmaceutical compositions containing them, and methods of using them, including methods for treating substance addiction, panic disorder, anxiety, post-traumatic stress disorder, pain, depression, seasonal affective disorder, an eating disorder, or hypertension.

Halo-substituted piperidines as orexin receptor modulators

The invention can provide compounds, analogs of blebbistatin, effective and selective inhibitors of nonmuscle myosin II relative to cardiac myosin II. Compounds can be used in the method of treating a disease, disorder, or medical condition in a patient, comprising modulating myosin II ATPase, such as treatment of substance abuse relapse disorder, or of renal disease, cancer and metastasis, benign prostate hyperplasia, hemostasis or thrombosis, nerve injury including retinal damage, lung fibrosis, liver fibrosis, arthrofibrosis, wound healing, spinal cord injury, periodontitis, glaucoma and immune-related diseases including multiple sclerosis; or wherein the disease, disorder, or medical condition comprises addiction including abuse of or addiction to anything classified as a Substance-Related or Addictive Disorder in the Diagnostic and Statistical Manual of Mental Disorders (DSM), such as, but not limited to, cocaine, opioids, amphetamines, ethanol, cannabis/marijuana, nicotine, and activities including gambling Compounds are of general formula (I) with substituents as defined herein.

Nonmuscle myosin II inhibitors for substance use relapse

Uncoupling of respiration is a well-recognized process that increases respiration and heat production in cells. Provided herein are chemical uncouplers of respiration that are compounds of Formula (I). Also provided are methods for preventing or treating metabolic disorders and modulating metabolic processes using compound of Formula (I).

Chemical uncouplers of respiration and methods of use thereof

The present invention provides compounds, pharmaceutical compositions and methods for treating and/or preventing a metabolic condition, such as diabetes.

Selective inhibition of gluconeogenic activity

The invention is directed to a method of inhibiting, within a living cell, the interaction between NF-&#x3ba;B essential modulator ('NEMO') with I&#x3ba;B kinase-&#x3b2; (IKK-&#x3b2;) at the NEMO binding domain (NBD), comprising exposing the cell to an effective amount or concentration of a compound of the invention, a NEMO-binding domain analog (NBDA). The invention is further directed to a method of treating a condition in a patient, wherein inhibiting the interaction between NF-&#x3ba;B essential modulator ('NEMO') with I&#x3ba;B kinase-&#x3b2; (IKK-&#x3b2;) at the NEMO binding domain (NBD) is medically indicated, comprising administering to the patient an effective dose of a compound of the invention. Conditions that can be treated by a method of the invention includes muscular dystrophy, asthma, inflammatory bowel disease, multiple sclerosis, Parkinson's Disease, arthritis, diabetes, graft versus host disease, accelerated aging, heart ischemia, cancer, UV-induced skin damage, or an age-related pathology.

Small molecule analogs of the nemo binding peptide

The invention provides methods of treatment of a progressive bone disease, such as osteoporosis, Paget's Disease, multiple myeloma, or hyperparathyroidism, comprising administration of an effective amount of a non-agonist PPARG modulator to a patient afflicted with the disease.

PPARG modulators for the treatment of osteoporosis

The present application relates to certain difluoropyrrolidine compounds, pharmaceutical compositions containing them, and methods of using them, including methods for treating substance addiction, panic disorder, anxiety, post-traumatic stress disorder, pain, depression, seasonal affective disorder, an eating disorder, or hypertension.

Difluoropyrrolidines as orexin receptor modulators

PPARG modulators for treatment of osteoporosis

The present invention is directed to compounds that modulate the bioactivity of an orexin receptor such as OXor OX, or both; to pharmaceutical compositions and combinations comprising a compound of the invention; to methods of treatment of malconditions in patients wherein modulation of an orexin receptor is medically indicated; and to methods of preparation of compounds of the invention. For example, orexin receptor-modulatory compounds of the present invention can be used in treatment of an eating disorder, obesity, alcoholism or an alcohol-related disorder, drug abuse or addiction including addiction to cocaine, opiates, amphetamines, or nicotine, a sleep disorder, a cognitive dysfunction in a psychiatric or neurologic disorder, depression, anxiety, panic disorder, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's chorea, headache, migraine, pain, gastrointestinal diseases, epilepsy, inflammations, immune-related diseases, endocrine-related diseases, cancer, hypertension, behavior disorder, mood disorder, manic depression, dementia, sex disorder, psychosexual disorder, or renal disease.

Substituted prolines/piperidines as orexin receptor antagonists

The invention provides small molecule modulators of retinoic acid receptor-related orphan receptors such as ROR&#x3b1;, ROR&#x3b2;, or ROR&#x3b3;, of formula with the variable atoms as defined herein and Rcomprising a hydroxyl- or alkoxyl-substituted fluoroalkyl group. Compounds of the invention can be effective modulators at concentrations ineffective to act on LXR receptors, or on other nuclear receptors, or other biological targets. Methods of modulation the RORs and methods of treating metabolic disorders, immune disorders, cancer, and CNS disorders wherein modulation of an ROR is medically indicated are also provided.

Modulators of the nuclear hormone receptor ROR

Substituted prolines / piperidines as orexin receptor antagonists

Growing community of inventors

Atlantic Highlands, NJ, United States of America

Theodore M Kamenecka