Mitotix, Inc.

Ariad Pharmaceuticals, Inc.

Ariad Gene Therapeutics, Inc.

Guillaume Cottarel

Veronique Damagnez

Vivian Berlin

Giulio Draetta

Maria Isabel Chiu

Mark Rolfe

Jens W Eckstein

Marie Isabel Chiu

The present invention relates to the discovery of novel proteins of mammalian origin which are immediate downstream targets for FKBP/rapamycin complexes.

Immunosuppressant target proteins

The present invention relates to the discovery of novel proteins of mammalian origin which are immediate downstream targets for FKBP/rapamycin complexes and provides, e.g., isolated polypeptides, nucleic acids encoding such, antibodies, screening methods, and diagnostic and therepeutic methods.

The present invention makes available assays and reagents for identifying anti-proliferative agents, such as mitotic and meiotic inhibitors. The present assay provides a simple and rapid screening test which relies on scoring for positive cellular proliferation as indicative of anti-mitotic or anti-meiotic activity, and comprises contacting a candidate agent with a cell which has an impaired cell-cycle checkpoint and measuring the level of proliferation in the presence and absence of the agent. The checkpoint impairment is such that it either causes premature progression of the cell through at least a portion of a cell-cycle or inhibition of normal progression of the cell through at least a portion of a cell-cycle, but can be off-set by the action of an agent which inhibits at least one regulatory protein of the cell-cycle in a manner which counter-balances the effect of the impairment.

Assay and reagents for identifying anti-proliferative agents

The present invention relates to drug screening assays which provide a systematic and practical approach for the identification of candidate agents able to inhibit ubiquitin-mediated degradation of a cell-cycle regulatory protein, such as p53, p27, myc, fos, MAT.alpha.2, or cyclins. The invention further relates to novel ubiquitin-conjugating enzymes, and uses related thereto.

Ubiquitin conjugating enzymes

The present invention relates to the discovery of novel cell cycle regulatory proteins from the human pathogen Candida.

Nucleic acid encoding a Candida cell cycle regulatory protein, TYP1

The present invention concerns three ubiquitin-conjugating enzymes.

The present invention makes available assays and reagents for identifying anti-proliferative agents, such as mitotic and meiotic inhibitors, especially inhibitors of cdc25 phosphatase. The present assay provides a simple and rapid screening test which relies on scoring for positive cellular proliferation as indicative of anti-mitotic or anti-meiotic activity, and comprises contacting a candidate agent with a cell which has an impaired cell-cycle checkpoint and measuring the level of proliferation in the presence and absence of the agent. The checkpoint impairment is such that it either causes premature progression of the cell through at least a portion of a cell-cycle or inhibition of normal progression of the cell through at least a portion of a cell-cycle, but can be off-set by the action of an agent which inhibits at least one regulatory protein of the cell-cycle in a manner which counter-balances the effect of the impairment.

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West Roxbury, MA, United States of America

Guillaume Cottarel