University System of Maryland

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

University of Texas System

Cornell University

Case Western Reserve University

Stc.unm

Albert Einstein College of Medicine

University Health Network

Gen1e Lifesciences Inc.

Alexander D MacKerell, Jr

Paul S Shapiro

Jeffrey D Hasday

Steven Fletcher

Alan Edward Tomkinson

Barbara Dziegielewska

Shijun Zhong

Gerald M Wilson

Ari Matthew Melnick

Fengtian Xue

Erik De Leeuw

France Carrier

Helen Xi Chen

David J Weber

Olgun Guvench

Adam Galan

Ritu Lal

Rae Matsumoto

Rakesh K Srivastava

Andrew Coop

Antonino Passaniti

Gilbert Privé

Sharmila Shankar

Leandro Carlos A Cerchietti

Mariano G Cardenas

Wanli Smith

Cheng-Kui Qu

Wen-Mei Yu

Xi Chen

Joseph Markowitz

Wenbo Yu

Chakk Ramesha

The compound 1,1-dioxido-2,3-dihydrothiophen-3-yl 4-phenoxybenzenesulfonate, pharmaceutical compositions thereof, and use of the compound and the pharmaceutical compositions for treating cancer and pulmonary diseases are disclosed.

Inhibitors of extracellular signal-regulated kinase

Compounds that inhibit p38α MAPK protein, and methods of using the same, are provided for treating or preventing diseases such as cancer or inflammatory diseases.

Non-ATP/catalytic site p38 mitogen activated protein kinase inhibitors

Non-catalytic substrate-selective p38alpha-specific MAPK inhibitors with endothelial-stabilizing and anti-inflammatory activity, and methods of use thereof

Non-catalytic substrate-selective p38α-specific MAPK inhibitors with endothelial-stabilizing and anti-inflammatory activity, and methods of use thereof

Compounds that inhibit p38&#x3b1; MAPK protein, and methods of using the same, are provided for treating or preventing diseases such as cancer or inflammatory diseases.

Non-ATP/catalytic site p38 Mitogen Activated Protein Kinase inhibitors

Provide herein are compounds with a general chemical structure of: Substituents Rand Rindependently are H, Cl, F, Br, CH, CF, SH, &#x2014;N(Calkyl), &#x2014;NHC(O)Calkyl, or &#x2014;NHC(O)Ccycloalkyl, substituent Ris H or Calkyl and R4 is a bridged cycloalkene such as a bridged cyclohexene or a bridge-substituted cyclohexene. The compounds are therapeutics to treat a cancer, such as breast cancer, or metastatic cancers, to inhibit RUNX2 activity, such as protein expression, in a cancer cell and to increase survival of a subject with breast cancer.

RUNX2 transcription factor inhibitors and uses thereof

Provided herein are protein translation inhibitors and pharmaceutical compositions thereof that bind to an RNA Recognition motif in heterogeneous ribonucleoprotein A18 to inhibit binding to mRNA transcripts thereby inhibiting protein synthesis. Also provided is a method for treating a cancer by administering a pharmaceutically acceptable amounts of at least one of the protein translation inhibitors.

Protein translation inhibitors and uses thereof

Non-catalytic substrate-selective, p38&#x3b1;-specific MAPK inhibitors with endothelial-stabilizing and anti-inflammatory activity, and methods of use thereof

The invention describes an explicit solvent all-atom molecular dynamics methodology (SILCS: Site Identification by Ligand Competitive Saturation) that uses small aliphatic and aromatic molecules plus water molecules to map the affinity pattern of a large molecule for hydrophobic groups, aromatic groups, hydrogen bond donors, and hydrogen bond acceptors. By simultaneously incorporating ligands representative of all these functionalities, the method is an in silico free energy-based competition assay that generates three-dimensional probability maps of fragment binding (FragMaps) indicating favorable fragment:large molecule interactions. The FragMaps may be used to qualitatively inform the design of small-molecule ligands or as scoring grids for high-throughput in silico docking that incorporates both an atomic-level description of solvation and the large molecule's flexibility.

Method for binding site identification by molecular dynamics simulation (silcs: site identification by ligand competitive saturation)

The invention provides compositions and methods for blocking the BCL6 BTB domain with small molecule, non-peptide compounds as disclosed and claimed herein. BCL6 is a transcriptional repressor of the BTB-POZ (brie a brae, tramtrack, broad complex/pox virus zincfinger) family of proteins. It is required for normal development of germinal center (GC) B-cells and is also the most commonly involvedoncogene in diffuse large B-celllymphomas (DLBCLs), and constitutive expression of BCL6 in GC B-cells causes DLBCL in mice.

BCL6 inhibitors as anticancer agents

Methods for treating cancer using compounds that inhibit human DNA ligases. Methods for using compounds that inhibit human DNA ligases to provide insights into the reaction mechanisms of human DNA ligases, for example to identify the human DNA ligase involved in different DNA repair pathways. Screening methods for compounds that inhibit human DNA ligases.

Compounds that inhibit human DNA ligases and methods of treating cancer

Compounds, and methods of using the same, are provided as therapies for the treatment leucine-rich repeat kinase-2 (LRRK2)-related disorders including, but not limited to, neurodegenerative and neuroinflammatory disorders, such as Parkinson's Disease.

LRRK2 GTP binding inhibitors for treatment of Parkinson's disease and neuroinflammatory disorders

An opioid narcotics used for the treatment of moderate-to-severe pain that primarily exert their analgesic effects through &#x3bc; receptors. Although, traditional &#x3bc; agonists can cause undesired side effects, including tolerance, addition of &#x3b4; antagonists can attenuate said side effects. The present invention includes 4a,9-dihydroxy-7a-(hydroxymethyl)-3-methyl-2,3,4,4a,5,6-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (UMB 425) a 5,14-bridged morphinan-based orvinol precursor, along with analogs of morphine, dihydromorphine, hydromorphone, codeine, dihydrocodeine, hydrocodone and ethylmorphine. Although UMB 425 lacks &#x3b4;-specific motifs, conformationally sampled pharmacophore models for &#x3bc; and &#x3b4; receptors predict it to have efficacy similar to morphine at &#x3bc; receptors and similar to naltrexone at &#x3b4; receptors, due to the compound sampling conformations in which the hydroxyl moiety interacts with the receptors similar to orvinols. UMB 425 exhibits a mixed &#x3bc; agonist/&#x3b4; antagonist profile as determined in receptor binding. UMB 425 has mixed &#x3bc; agonist/&#x3b4; antagonist properties in vitro that translate to reduced tolerance liabilities in vivo.

Mixed &#x3bc; agonist/ &#x3b4; antagonist opioid analgesics with reduced tolerance liabilities and uses thereof

Disclosed are compositions and methods for treating and/or preventing infections in mammals, by administering to a mammal a therapeutically effective amount of at least one defensin-like molecule, e.g., in a composition that includes such molecule. Also disclosed are kits that include such molecules, or compositions that include such molecules, as well as instructions for using such molecules to treat a mammal.

Defensin-like molecules as novel antimicrobial agents

Growing community of inventors

Baltimore, MD, United States of America

Alexander D MacKerell, Jr