Other

Merck Frosst Canada, Inc.

Merck Frosst Canada & Co.

Mcgill University

Brian P Kennedy

Michel L Tremblay

Cameron Black

Wanda A Cromlish

George Zogopoulos

Claudia Penafuerte

Matthew Feldhammer

Joseph A Mancini

Gary P O'Neill

Philip J Vickers

Elizabeth Wong

Michael Gresser

Richard W Friesen

Vouy-Linh Truong

Anthony Ford-Hutchinson

Sylvie Desmarais

Chidambaran Ramachandran

Kathryn Skorey

Mounib Elchebly

Chidambaram Ramachandran

Paul Payette

Don Nicholson

Sheldon Crane

The invention encompasses the novel class of compounds represented by the Formula (I) below, which are inhibitors of the TC-PTP enzyme. The invention also encompasses pharmaceutical compositions which include the compounds shown above and methods of treating or preventing TC-PTP mediated diseases, including cancer, via their use in the activation of antigen-presenting cells, like dendritic cells, for applications in the immunotherapeutic treatment of diseases. 

TC-PTP inhibitors as APC activators for immunotherapy

The invention discloses a human cyclooxygenase-2 cDNA, a human cyclooxygenase-2 and assays for preferentially and independently measuring cyclogenase-2 or cyclooxygenase-1 activity present in a given sample.

Human cyclooxygenase-2 cDNA and assays for evaluating cyclooxygenase-2 activity

The present invention provides mice that have had their PTP-1B genes disrupted by targeted homologous recombination. The mice have no detectable PTP-1B protein, yet appear to be physiologically normal. However, in the fed state on a normal diet, the mice have half the level of circulating insulin as their wild-type littermates. In glucose and insulin tolerance tests, the mice show an increased insulin sensitivity. When fed a high fat, high carbohydrate diet, the mice show a resistance to weight gain as compared to their wild-type littermates. Methods making the mice and cell lines derived from the mice are also provided. The present invention also provides methods of identifying inhibitors of the enzymatic activity of PTP-1B as well as inhibitors identified by such methods.

Protein tyrosine phosphate-1B (PTP-1B) deficient mice and uses thereof

Intact cell assay for protein tyrosine phosphatases using recombinant baculoviruses

Disclosed is a binding assay for proteases and phosphatases, which contain cysteine in their binding sites or as a necessary structural component for enzymatic binding. The sulfhydryl group of cysteine is the nucleophilic group in the enzyme's mechanistic proteolytic and hydrolytic properties. The assay can be used to determine the ability of new, unknown ligands and mixtures of compounds to competitively bind with the enzyme versus a known binding agent for the enzyme, e.g., a known enzyme inhibitor. By the use of a mutant form of the natural or native wild-type enzyme, in which serine, or another amino acid, e.g., alanine, replaces cysteine, the problem of interference from extraneous oxidizing and alkylating agents in the assay procedure is overcome. The interference arises because of oxidation or alkylation of the sulfhydryl, --SH (or --S.sup.-), in the cysteine, which then adversely affects the binding ability of the enzyme. Specifically disclosed is an assay for tyrosine phosphatases and cysteine proteases, including caspases and cathepsins, e.g., Cathepsin K(O2), utilizing scintillation proximity assay (SPA) technology. The assay has important applications in the discovery of compounds for the treatment and study of, for example, diabetes, immunosuppression, cancer, Alzheimer's disease and osteoporosis. The novel feature of the use of a mutant enzyme can be extended to its use in a wide variety of conventional colorimetric, photometric, spectrophotometric, radioimmunoassay and ligand-binding competitive assays.

Prosphatase binding assay

Human cyclooxygenase-2 cDNA and assays for evaluating cyclooxygenase-2

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Kirkland, Canada

Brian P Kennedy