Cell Therapeutics, Inc.

Genentech, Inc.

Glenn C Rice

J Peter Klein

Jack W Singer

Gail E Underiner

Stuart L Bursten

Anil M Kumar

David W Leung

John Michnick

Paul A Brown

David V Goeddel

David J Porubek

Paul Woodson

Alistair J Leigh

Lance H Ridgers

There is disclosed a method for preventing tissue injury caused by tissue hypoxia and reoxygenation, comprising administering a compound that inhibits signal transduction by inhibiting cellular accumulation of linoleoyl phosphatidic acid (PA) through an inhibition of the enzyme LPAAT (lysophosphatidic acyltransferase).

Method for preventing tissue injury from hypoxia

Therapeutic compounds with at least one carboxylic acid, ester or amide-substituted side chain have the formula:

Methods for using therapeutic compounds containing xanthinyl

Method for treating diseases mediated by cellular proliferation in

Amino-alcohol substituted cyclic compounds

A method for treating a disease caused by an undesirable cell response mediated by a proliferative intracellular signaling pathway is provided wherein an effective amount of a compound is administered. The compound, resolved enantiomers, diastereomers, hydrates, salts, solvates and mixtures thereof, has the formula

Amine substituted xanthinyl compounds

Amino alcohol substituted cyclic compounds

A screening method for the selection of mutagenized proteins that are normally secreted by cells is described. The method includes the development of a cloning vector for the expression of secretory proteins as fusion proteins on the cell surface of transfected mammalian cells. The secreted protein is displayed on the cell surface by fusion with the glycophospholipid membrane anchor of decay accelerating factor (DAF). Tissue-type plasminogen activator (t-PA), which is normally secreted, is used as a model protein. PCR mutagenesis is used to generate random mutations within the Kringle 1 (K1) domain of t-PA. Fluorescence activated cell sorting (FACS) is employed to screen for t-PA mutants possessing a loss of an epitope to a specific Mab, whose nonlinear binding domains overlap with the t-PA clearance receptor contact regions novel t-PA mutants designated N115S, N1425S, and K159R were discovered by this method.

Method for making variant secreted proteins with altered properties

There is disclosed a method for reversing the multiple drug resistant (MDR) phenotype in tumors insensitive to hydrophobic chemotherapeutic drugs due to over expression of mdr-1, comprising administering an effective amount of a long chain amino alcohol compound. There is further disclosed a method for preventing the development of MDR during cancer chemotherapy treatments, comprising administering during cancer chemotherapy treatments an effective amount of a long chain amino alcohol compound.

Method for reversing multiple drug resistant phenotype

Cell signaling inhibitors

Compounds of the formula ##STR1## including the resolved enantiomers and/or diastereomers and mixtures thereof wherein each of one or two R is independently ##STR2## wherein n is 1-16 and R' is H or alkyl(1-4C); and wherein each remaining R is independently H, alkyl(1-6C), alkenyl(1-6C) or benzyl; an wherein said alkyl or alkenyl may be substituted by a hydroxyl, halo, or dimethylamino group, and/or interrupted by an oxygen atom, are useful in modulating the effects of internal and external stimuli on cells by reversing the effects of these stimuli on the short-term secondary messenger pathways. In particular, the compounds lower elevated levels of unsaturated, non-arachidonate phosphatidic acid (PA) and diacylglycerol (DAG) derived from said PA within seconds of the primary stimulus and their contact with said cells. The modulatory effect depends on the nature of the target cell and the stimulus applied.

Substituted epoxyalkyl xanthines

Growing community of inventors

Seattle, WA, United States of America

Glenn C Rice