Pharmacopeia Inc.

Pharmacopeia Drug Discovery, Inc.

Pharmacopela Drug Discovery, Inc.

James Inglese

Jonathan J Burbaum

Shawn David Erickson

Bassam Damaj

J Fraser Glickman

John J Baldwin

Roland Ellwood Dolle

Koc-Kan Ho

Dirk Leysen

Jeffrey John Letourneau

Jaap Van Der Louw

Michael H J Ohlmeyer

Gregory L Kirk

Steven G Kultgen

Christopher Mark Riviello

Adolph C Bohnstedt

Paolo Giovanni Martino Conti

Maria Webb

Daniel Chelsky

Kenneth C Appell

Thomas Dy Chung

Ilana L Stroke

Philippe Samama

Joseph Fraser Glickman

Compounds containing the pyrimidine nucleus and their use to treat diseases and conditions related to inappropriate Interleukin-8 receptor activity are disclosed. The compounds are of the formula IIn these compounds, Q is preferably unsubstituted and substituted heterocyclyl; U is usually hydrogen or fluorine; and V is preferably hydrogen, halogen, alkyl, &#x2014;O&#x2014;alkyl or &#x2014;S-alkyl. A representative example is:

Pyrimidine derivatives as IL-8 receptor antagonists

Compounds that selectively inhibit inappropriate kinase activities and methods for their preparation are disclosed. In one embodiment, the compounds are represented by Formula I,As selective inhibitors of inappropriate kinase activities, the compounds of the present invention are useful in the treatment of conditions associated with such activity, including, but not limited to, inflammatory and autoimmune responses, diabetes, asthma, psoriasis, inflammatory bowel disease, transplantation rejection, and tumor metastasis. Also disclosed are methods of inhibiting inappropriate kinase activities and methods of treating conditions associated with such activities.

Pyrimidine and triazine kinase inhibitors

A method for determining the level of tyrosine kinase activity in a biological sample is disclosed. The method employs an anti-phosphotyrosine antibody as both the capture agent and the detecting agent. The detecting antibody is labeled with a fluorescent label, for instance, Cy5, Cy5.5 or Cy7 or a lanthanide ion, such as europium, as the signal generating entity. The method is particularly well suited to high throughput screening, for example, for compounds which modulate tyrosine kinase activity.

Fluorescent capture assay for kinase activity employing an anti-phosphotyrosine antibody as both the capture agent and detecting agent

A method for determining the level of tyrosine kinase activity in a biological sample is disclosed. The method employs an anti-phosphotyrosine antibody as both the capture agent and the detecting agent. The detecting antibody is labeled with a lanthanide ion, such as europium, as the signal generating entity. The method is particularly well suited to high throughput screening, for example, for compounds which modulate tyrosine kinase activity.

Fluorescent capture assay for kinase activity employing anti-phosphotyrosine antibodies as capture and detection agents

Incorporation of phosphorylation sites

The present invention encompasses polypeptides that comprise a chemokine receptor binding sequence and are useful in determining the affinity of a compound for a chemokine receptor. Substitution of one of the amino acids of the C-terminal region of the polypeptide with a cysteine enables the polypeptide to be detectably labelled without loss of receptor binding activity and without the problems inherent in radioiodine labelling. Methods for use of the polypeptides in competitive binding assays are also disclosed.

Site-specific bioconjugates of chemokines and their use in assays

A homogeneous high throughput assay is described which screens compounds for enzyme inhibition, or receptor or other target binding. Inhibition (or binding) by the library compounds causes a change in the amount of an optically detectable label that is bound to suspendable cells or solid supports. The amounts of label bound to individual cells or solid supports are microscopically determined, and compared with the amount of label that is not bound to individual cells or solid supports. The degree of inhibition or binding is determined using this data. Confocal microscopy, and subsequent data analysis, allow the assay to be carried out without any separation step, and provide for high throughput screening of very small assay volumes using very small amounts of test compound.

High-throughput assay

Growing community of inventors

Lansdale, PA, United States of America

James Inglese