University System of Maryland

University of Pittsburgh

Gen1e Lifesciences Inc.

Mcdaniel College

Steven Fletcher

Alexander D MacKerell, Jr

Paul S Shapiro

Jeffrey D Hasday

Alexander MacKerell

Erik De Leeuw

Jamal Chauhan

Dana Victor Ferraris

Ritu Lal

Adam Galan

Rena S Lapidus

Edward A Sausville

Nicolas Paul Sluis-Cremer

Brandon Carter-Cooper

Eric J Sundberg

Ashkan Emadi

Yohei Doi

Erik H Klontz

Brandon Drennen

Chakk Ramesha

Maryanna Lanning

Adam Daniel Tomich

Lijia Chen

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

Mcl-1 selective inhibitors, Bcl-2 selective inhibitors, and Mcl-1/Bcl-2 dual inhibitors and methods of using the same for the treatment of disease are disclosed.

Carboxylic acid, acyl sulfonamide and acyl sulfamide-derivatized bicyclic aza-heteroaromatics as selective Mcl-1 inhibitors and as dual Mcl-1/Bcl-2 inhibitors

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

The invention relates to new amino dimeric naphthoquinone compounds with antileukemic activity. Compounds of the invention demonstrated increased aqueous solubility compared to previously available dimeric naphthoquinones and potent nanomolar inhibition of cell survival in AML cells. Preferred compounds contained an aziridine or a secondary amino alcohol pharmacophore.

Aziridinyl and amino dimeric naphthoquinone compounds and use for acute myeloid leukemia

Compounds, pharmaceutical compositions, and methods for reversing fosfomycin resistance are disclosed. Embodiments of the disclosed compounds inhibit fosfomycin-inhibiting enzymes. Some embodiments of the compounds are FosA inhibitors. The disclosed pharmaceutical compositions include (i) fosfomycin or a pharmaceutically acceptable salt thereof and (ii) a compound, or a pharmaceutically acceptable salt thereof, which inhibits a fosfomycin-inhibiting enzyme. A method of inhibiting growth of a fosfomycin-resistant bacterium includes contacting the bacterium with (i) fosfomycin or a pharmaceutically acceptable salt thereof and (ii) an effective amount of a disclosed compound or a pharmaceutically acceptable salt thereof.

Reversal of fosfomycin resistance

Newly synthesized derivatives of BAS00127538 have been discovered to possess antibiotic activity and to combat resistant bacterial strains. Compounds and pharmaceutical compositions containing these compounds are described, and are based on a generic scaffold structure. Synthetic methods and methods of using the compounds also are described. Preferred compound 6jc48-1 ((E)-2,4-bis(4-bromophenyl)-6-(4-(dimethyl-amino)styryl)pyrylium boron tetrafluoride salt) binds to Lipid II with high affinity, has markedly reduced cytotoxicity than BAS00127538, and retains activity against drug-resistant strains of. It is stable in plasma, has dramatically improved pharmacokinetic and pharmacodynamics properties, and possesses in vivo efficacy in a mouse model of sepsis. 

Small molecule lipid II inhibitors

Newly synthesized derivatives of BAS00127538 have been discovered to possess antibiotic activity and to combat resistant bacterial strains. Compounds and pharmaceutical compositions containing these compounds are described, and are based on a genetic scaffold structure. Synthetic methods and methods of using the compounds also are described. Preferred compounds bind to Lipid II with high affinity, have markedly reduced cytotoxicity compared to BAS00127538, and retain activity against drug-resistant strains of Enterococci. They are stable in plasma, have dramatically improved pharmacokinetic and pharmacodynamics properties, and possess in vivo efficacy in a mouse model of sepsis. 

Compounds that inhibit Myeloid Cell Leukemia-1 (Mcl-1) oncoprotein, and methods of using the same, are provided for treating disease.

Small molecule inhibitors of the MCL-1 oncoprotein and uses thereof

The present invention relates compounds and compositions for interfering with the association of Myc and Max. These compounds and compositions are useful in methods for inhibiting growth or proliferation of a cell. Methods of inhibiting growth or proliferation of a cell comprise contacting the cell with an amount of a compound that interferes with Myc and Max association effective to inhibit growth or proliferation of the cell. The compounds exhibit increased inhibitory activity against c-Myc relative to the known c-Myc inhibitor small-molecule benzofurazan N-([1,1'-biphenyl]-2-yl)-7-nitrobenzo[c][1,2,5]oxadiazol-4-amine (10074-G5).

Potent analogues of the C-Myc inhibitor 10074-G5 with improved cell permeability

A compound, having the formula A-1:  Wherein Rand Rare defined herein. Methods of using the compound and compositions containing the compound are provided.

Non-ATP dependent inhibitors of extracellular signal-regulated kinase (ERK)

Small-molecule scaffolds based on 1,2-diphenylacetylene that accurately replicate the spatial and angular projections of several side chains on both faces of an &#x3b1;-helix, specifically the i and i+7 side chains on one face, and the i and i+2 side chains on the other. The amphipathic &#x3b1;-helix mimetic can be used to disrupt disease-promoting protein-protein interactions that are mediated by &#x3b1;-helices.

Growing community of inventors

Baltimore, MD, United States of America

Steven Fletcher