University of Pittsburgh

Other

Billy W Day

Neil Hukriede

Dennis Patrick Curran

Waikok Michael Tsang

Raghavan Balachandran

Vasiliy N Korotchenko

Youseung Shin

Peter Wipf

Nakyen Choy

Thomas E Smithgall

Lee A McDermott

Tiffany Turner

Charitha Madiraju

Lori Ann Emert-Sedlak

Richard J McClure

John S Lazo

Jay W Pettegrew

Kanagasabai Panchalingam

Prema Chandrasekhar Iyer

Paul Edward Floreancig

Weixiang Dai

Jielu Zhao

Ronald P Trible

Jean-Hugues Fournier

Shuangyi Wan

John Mancuso

Arndt Bruckner

Fanghui Wu

Yoshikazu Fukui

Jonathan T Reeves

Toshiaki Kodama

Compounds and compositions are provided that inhibit histone deacylase activity and which expand renal progenitor cell populations and improve kidney function in a damaged kidney. Methods of use of the compounds and compositions are provided.

Class of HDAC inhibitors expands the renal progenitor cells population and improves the rate of recovery from acute kidney injury

Disclosed herein are embodiments of a compound capable of treating HIV. In particular disclosed embodiments, the compound is capable of inhibiting Nef, such as by acting as antagonists of HIV Nef function. Also disclosed are embodiments of a method of making the compound, embodiments of a method of using the compound, and embodiments of a method of identifying HIV Nef antagonists. The disclosed compound may be used alone or in combination with other pharmacologically active agents in order to promote reducing drug resistance and/or cumulative toxicity.

Compounds for treating HIV and methods for using the compounds

Compounds that stimulate fibroblast growth factor production, and thus cell growth are provided. Also provided are compositions comprising the compounds and methods of using the compounds. The compounds can be used to treat wounds, to expand cell populations, such as hematopoietic cells, or to grow tissue in vitro, among other uses.

Small molecule inhibitors of Dusp6 and uses therefor

Compounds that include a pederin, psymberin or pederin/psymberin chimera scaffold. The pederin scaffold includes a substituent at the C10 and/or C13 position that may include a linker that may be conjugated to a targeting moiety. The psymberin scaffold includes a substituent at the C8 and/or C11 positions that may include a linker that may be conjugated to a targeting moiety. The pederin/psymberin chimera scaffold includes a substituent at the C10 and/or C13 position that may include a linker that may be conjugated to a targeting moiety. The pederin, psymberin or pederin/psymberin chimera scaffold may be modified to include substituents at positions other than the C10 or C13 of pederin, or the C8 and C11 of psymberin.

Pederin and psymberin agents

Drug candidates for inhibition of HIV-I replication can target Src family kinases (SFK), such as Hck, that interact with Nef protein of the virus. Compounds characterized by such inhibitory activity were identified via an assay for kinase activity of an SFK in a Nef:SFK complex. Illustrative of inhibitors identified using the kinase assay are various 2,3-diaminoquinaxolines and furo[2,3-d]pyrimidines. The inventive inhibitors were found to arrest HIV-I viral replication in vitro.

Targeting an HIV-1 nef-host cell kinase complex

Analogs of discodermolide and dictyostatin-1, intermediates therefor and methods of synthesis thereof

Compounds, compositions and methods for the diagnosis of Alzheimer's disease. Synthesized Glycerophosphocholine (GPC) may be used as a diagnostic aid to measure progression of Alzheimer's disease. GPC is a membrane phospholipid metabolite that is capable of binding specifically to the &#x3b2;-turn of beta amyloid (A&#x3b2;) peptide. Compounds including non-radioactive, paramagnetic, and radioactive derivatives of GPC are presented. These compounds possess similar binding properties to original GPC molecules and are useful in medical magnetic resonance imaging and/or positron emission tomography applications. By employing these radiological techniques in conjunction with the compositions of the present invention, the diagnosis and assessment of the progression of Alzheimer's disease may be achieved.

Compounds, compositions and methods for medical imaging of neuropsychiatric disorders

Dictyostatin and its analogs show great promise as new anticancer agents. The present invention provides dictyostatin analogs, synthetic intermediates for the synthesis of dictyostatin analogs, and synthetic methods for the synthesis of such analogs and intermediates. Dictyostatin analogs can have the following structure or its enantiomer wherein Ris H, an alkyl group, an aryl group, an alkenyl group, an alkynyl group, or a halogen atom; Ris H, a protecting group, an alkyl group, a benzyl group, a trityl group, &#x2014;SiRRR, CHOR, or COR; R, Rand Rare independently an alkyl group or an aryl group; Ris an alkyl group, an aryl group, an alkoxylalkyl group, &#x2014;RSiRRRor a benzyl group, wherein Ris an alkylene group; Ris an alkyl group, an allyl group, a benzyl group, an aryl group, an alkoxy group, or &#x2014;NRR, wherein Rand Rare independently H, an alkyl group or an aryl group; Ris (CH)where n is and integer in the range of 0 to 5, &#x2014;CHCH(CH)&#x2014;, &#x2014;CH&#x2550;CH&#x2014;, &#x2014;CH&#x2550;C(CH)&#x2014;, or &#x2014;C&#x2261;C&#x2014;; Ris wherein Ris H, a protecting group, an alkyl group, a benzyl group, a trityl group, &#x2014;SiRRR, CHOR, or COR; Ris H, a protecting group, an alkyl group, a benzyl group, a trityl group, &#x2014;SiRRR, CHOR, or COR, or Rand Rtogether form a portion of six-membered acetal ring incorporating CRR; Rand Rare independently H, an alkyl group, an aryl group or an alkoxyaryl group; and Ris H or OR, wherein Ris H, a protecting group, an alkyl group, an aryl group, a benzyl group, a trityl group, &#x2014;SiRRR, CHOR, or COR; provided that the compound is not dictyostatin 1.

Analogs of dictyostatin, intermediates therefor and methods of synthesis thereof

A compound of the following structure: wherein Ris H, an alkyl group, an aryl group, an alkenyl group, an alkynyl group, or a halogen atom;

Oxidative cyclization of bis-naphthyl ethers allows concise total syntheses of palmarumycin CP and deoxypreussomerin A in 8-9 steps and 15-35% overall yield from 5-hydroxy-8-methoxy-1-tetralone. A small library of palmarumycin analogs was created. Biological evaluation of these naphthoquinone spiroketals against MCF-7 and MDA-MB-231 human breast cancer cells revealed several low-micromolar growth inhibitors. A number of the analogs inhibit the thioredoxin&mdash;thioredoxin reductase system.

Syntheses and methods of use of new antimitotic agents

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Pittsburgh, PA, United States of America

Billy W Day