University of Pittsburgh

University of Virginia Patent Foundation

John S Lazo

Peter Wipf

April Cunningham

Robert L Rice

Joel Byron Nelson

Zhou Wang

Paul A Johnston

Minh Bao Nguyen

Ettore Rastelli

Nikhil Tasker

Elizabeth Sharlow

Said M Sebti

Joel S Greenberger

Billy W Day

Valerian Kagan

Michael Wayne Epperly

Edward V Prochownik

Jianfei Jiang

Christine Giap

Joseph M Salamoun

Xiaoying Yin

Jehangir S Mistry

Jitesh P Jani

Elizabeth R Sharlow

Minh Mindy Bao Nguyen

Kelley E McQueeney

Peter McDonald

The disclosure provides compounds that inhibit protein tyrosine phosphatase, such as protein tyrosine phosphatase 4 A3 (PTP4A3). The disclosure also provides pharmaceutical compositions, uses, and methods of using the compounds, such as in the treatment of cancers.

In-flow photooxygenation of aminothienopyridinones generates novel PTP4A3 phosphatase inhibitors

The disclosure provides compounds that inhibit protein tyrosine phosphatase, such as protein tyrosine phosphatase 4A3 (PTP4A3). The disclosure also provides pharmaceutical compositions, uses, and methods of using the compounds, such as in the treatment of cancers. (I), wherein X is O or NH.

In-flow photooxygenation of aminothienopyridinones generates PTP4A3 phosphatase inhibitors

The invention provides protein tyrosine phosphatase inhibitor compounds, Their pharmaceutical compositions, uses, and methods of use, such as in the treatment of various cancers, and process for making the compounds. Also disclosed is an improved synthesis of protein tyrosine phosphatase inhibitor and precursor compound thienopyridone (5).

Inhibitors of PTP4A3 for the treatment of cancer

A method for treating prostate cancer in a subject, comprising administering a therapeutically effective amount of at least one agent to the subject, wherein the agent is selected from: 

Small molecules targeting androgen receptor nuclear localization and/or level in prostate cancer

A method for treating prostate cancer in a subject, comprising administering a therapeutically effective amount of at least one agent to the subject, wherein the agent is selected from: wherein Ris an aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl, substituted heterocycloalkyl, alkoxy, aryloxy, a silyl-containing group, a boryl-containing group, a phosphine-containing group, amino, a thio-containing group, a seleno-containing group, halide, or a nitro-containing group;

Provided herein are methods, for reducing, preventing, mitigating and treating damage caused by radiation. The methods comprise delivering a compound, as described herein, to a patient in an amount and dosage regimen effective to prevent, mitigate or treat damage caused by radiation or to mitigate apoptosis. The compounds comprise glyburide or other sulfonylurea hypoglycemic compounds or potassium channel inhibitors.

Radioprotective agents

The c-Myc oncoprotein, a helix-loop-helix-leucine zipper (HLH-ZIP) transcription factor, is frequently deregulated in human cancers. All known functions of c-Myc, including those pertaining to transformation, require that it heterodimerize with another HLH-ZIP protein, Max. Using a high throughput yeast-based assay, we identified seven low molecular weight substances that inhibit c-Myc-Max association. Each compound also prevented this interaction in vitro and inhibited the growth of c-Myc-expressing fibroblasts, although not of fibroblasts lacking c-Myc. Finally, short-term exposure of c-Myc over expressing fibroblasts to several of the compounds markedly reduced their in vivo tumorigenicity. These studies suggest that yeast-based assays can be used to identify inhibitors of protein-protein interactions and that these frequently function in mammalian cells. The signature specificities of each of the c-Myc-Max compounds identified here further suggest synergistic in vivo function.

Pharmacologic inhibition of Myc function

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

The present invention is directed to compounds having the formula: ##STR1## The invention further provides a method of making the compounds. The compounds are useful as inhibitors of protein phosphatases, for example PP1, PP2A, PP3, CDC25A and CDC25B. The invention is further directed to a method of inhibiting a protein phosphatase, a method of inhibiting cell proliferation, and pharmaceutical compositions comprising the subject compounds.

Phosphatase inhibitors and methods of use thereof

Peptidyl prodrugs of therapeutic agents having an activating function are sclosed. These therapeutic agents having activating functions include those having an amino, thiol, or hydroxyl function. Methods of making and using these prodrugs are also disclosed.

Peptidyl prodrugs and methods of making and using the same

A fluorescent-labelled bleomycin analog useful as a probe for measuring cellular uptake of bleomycin and bleomycin derivatives, including methods of making and using same. The analog may further be used as a therapeutic agent as well as a diagnostic tool.

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Pittsburgh, PA, United States of America

John S Lazo