Bristol-myers Squibb Compnay

Other

University of Utah Research Foundation

Craig R Fairchild

Francis Lee

Lukas C Amler

Peter Shaw

Fei Huang

Xia Han

Karen A Reeves

John E Leet

Stephen W Mamber

Chris M Ireland

Xiaohong Liu

Brent R Copp

Yuzuru Shimizu

The present invention relates to xanthone compounds isolated from the plantHochr. (Clusiaceae), a Madagascar plant, which are potent cytotoxic agents.

Cytotoxic xanthone compounds

The present invention describes polynucleotides that have been discovered to correlate to the relative sensitivity or resistance of cells, e.g., breast cell lines, to treatment with compounds that interact with and modulate, e.g., inhibit, protein tyrosine kinases, such as, for example, members of the Src family of tyrosine kinases, e.g., Src, Fgr, Fyn, Yes, Blk, Hck, Lck and Lyn, as well as other protein tyrosine kinases, including, Bcr-abl, Jak, PDGFR, c-kit and Eph receptors. These polynucleotides have been shown to have utility in predicting the resistance and sensitivity of breast cell lines to the compounds. Such polynucleotides comprise polynucleotide predictor or marker sets useful in methods of predicting drug response, and as prognostic or diagnostic indicators in disease management, particularly in those disease areas, e.g., breast cancer, in which signaling through one or more of the aforementioned Src tyrosine and protein tyrosine kinases is involved with the disease process.

Identification of polynucleotides for predicting activity of compounds that interact with and/or modulate protein tyrosine kinases and/or protein tyrosine kinase pathways in breast cells

Methods of using EPHA2 for predicting activity of compounds that interact with and/or modulate protein tyrosine kinases and/or protein tyrosine kinase pathways in breast cells

Naamidine A isolated from marine sponges is found to be selective in inhibiting the growth of tumor cells which are dependent upon epidermal growth factor for their growth, while showing acceptably low general cytotoxicity. Such selectivity was established through in vitro and in vivo comparative testing using tumor cells which over express EGF receptor cites. The in vivo tests used nude athymic mice that were implanted with squamous cells carcinoma.

Naamidine A extracted from sea sponges and methods for its use as an

Compound (1), isolated from a marine dinoflagellate, is a novel macrolide which has potent in vitro cytotoxicity against human colon carcinoma cell line HCT116 (IC.sub.50 =1.6 nM) and a multiple drug resistant subline. In addition, this compound has good in vivo antitumor activity against a P388 mouse leukemia (150% T/C).

Caribenolide I

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Yardley, PA, United States of America

Craig R Fairchild