The University of Texas System

University of Hawai'i

Wayne State University

Southwest Foundation for Biomedical Research

Other

University of Oklahoma

Virginia Commonwealth University

Utah State University

University of Richmond

Susan L Mooberry

April L Risinger

Thomas Hughes Corbett

Richard E Moore

Pemmaraju Narasimha Rao

James W Cessac

Gregory M Patterson

Jing Li

Frederick A Valeriote

Charles D Smith

Trimurtulu Golakoti

Jiangnan Peng

Bradley S Davidson

Tina L Tinley

Robert H Cichewicz

Nakul S Telang

Saikat Haldar

Thomas K Hemscheidt

Andrew J Robles

Cristina Rohena

James A Sikorski

John T Gupton

Ashutosh Tripathi

Chenxiao Da

Glen E Kellogg

Peter Houghton

Certain embodiments are directed to methods for treating Ewing family tumors (EFT) comprising administering an effective amount of altertoxin II to a subject having EFT.

Altertoxin II as a selective inhibitor of Ewing family of tumor cells

The invention provides epoxytaccalonolide microtubule stabilizers and their use as anti-proliferative microtubule stabilizing agents.

Taccalonolide microtubule stabilizers

The present invention provides polysubstituted pyrrole compounds, pharmaceutically effective salts, prodrugs, solvates and hydrates thereof, having antimitotic, antiproliferative and cytotoxic activity, activity against cells expressing the drug efflux protein, P-glycoprotein, or cells expressing the &#x3b2;-III isotype of tubulin and antitumor activity. Also provided are methods of utilizing these compounds for inhibiting the proliferation of cancer cells as well as their medical use, in particular for treating cancer, including drug resistant cancer.

Polysubstituted pyrroles having microtubule-disrupting, cytotoxic and antitumor activities and methods of use thereof

A method of inhibiting the proliferation of a hyperproliferative mammalian cell having a multiple drug resistant phenotype utilizing an amount of a laulimalide compound effective to disrupt the dynamic state of microtubule polymerization and depolymerization to arrest cell mitosis is disclosed, together with laulimalide compounds which find use in such method.

Laulimalide microtubule stabilizing agents

In accordance with the present invention, there have been identified extracts from a tropical plant that initiate paclitaxel-like microtubule bundling. Bioassay-directed purification yields the steroid taccalonolide A. Taccalonolide, like paclitaxel, initiates the formation of abnormal interphaes and mitotic microtubules. Cells treated with taccalonolide exhibit thick bundles of microtubules that appear to nucleate independent of the microtubule organizing center. Abnormal mitotic spindles consisting of multi-polar spindles are initiated by taccalonolide and resemble abnormal mitotic spindles found in the presence of paclitaxel. Like paclitaxel, taccalonolide causes the breakdown of the nucleus into micronuclei. Taccalonolide causes G2/M arrest, Bc1-2 phosphorylation and initiates an apoptotic cascade that includes the activation of caspase 3. Taccalonolide is an effective inhibitor of proliferation against both SK-OV-3 and MDA-MB-435 cell with ICvalues of 2.3 &#x3bc;M and 2.1 &#x3bc;M respectively. In contrast to paclitaxel, taccalonolide is effective against the multidrug resistant SKVLB-1 cellline and thus appears to be a poor substrate for P-glycoprotein-mediated transport. Although taccalonolide is almost equipotent with paclitaxel in its effects on cellular microtubules, it is much less potent than paclitaxel in its ability to initiate the polymerization of purified tubulin and microtubule protein. Taccalonolide A is the first microtubule stabilizing agent to be discovered from a plant since identification of the mechanism of action of paclitaxel and it is the first natural product steroid identified to have these cellular effects.

Taccalonolide microtubule stabilizing agents

The application discloses novel 2-alkoxyestradiol analogs which exhibit anti-proliferative properties, and methods of making and using such compounds to inhibit undesired cell proliferation and tumor growth. Additionally, methods are disclosed of treating diseases associated with undesired angiogenesis and undesired proliferation, and methods of treating infectious disease wherein the infectious agent is particularly susceptible to inhibition by agents that disrupt microtubule organization and function.

2-alkoxyestradiol analogs with antiproliferative and antimitotic activity

A cryptophycin compound is provided having the structure: ##STR1## Further provided are methods for producing novel cryptophycins from the Nostoc sp. of blue-green algae (cyanobacteria). Pharmaceutical compositions comprising novel cryptophycins are also provided, as are methods for using cryptophycins to inhibit the proliferation of hyperproliferative cells. Further provided are methods for using cryptophycins to inhibit the proliferation of hyperproliferative cells with drug resistant phenotypes, and to treat pathological conditions, such as neoplasia.

Cryptophycins

Growing community of inventors

San Antonio, TX, United States of America

Susan L Mooberry