The Scripps Research Institute

University of California

University of Pennsylvania

Scripps Clinic and Research Foundation

Edward F. Plow

Mark H. Ginsberg

Andrew L, Iii Frelinger

Mark H Ginsberg

Edward F Plow

Andrew L Frelinger, Iii

Ronald D Bowditch

Robert McMillan

Stanley E D'Souza

Timothy E O'Toole

Sanford Shattil

Charles G Cochrane

Alexander Groisman

John H Peters

Edgar Gutierrez

Joseph C Loftus

Kate Louise Wegener

Eugene Tkachenko

Edward F Flow

Christiane Kummer

Csilla Fenczik

Anthony William Partridge

Iain Campbell

Concepcion Zamarron

Iii Frelinger Andrew L

The present invention is directed to novel compounds that are able to inhibit the interaction of paxillin or its paralogues, including leupaxin or Hic-5, with alpha.4 integrin or its binding partners that regulate signaling events downstream of the paxillin-.alpha.4 interaction. The present invention further relates to methods for therapeutic use of such compounds and pharmaceutical compositions of such compounds for the treatment of a disease or condition.

Small molecule inhibitors of the &#x3b1;4-paxillin interaction

The specific molecular basis of the interaction between talin and integrin &#x3b2;has been defined. This specific interaction provides a new therapeutic target; agents that can disrupt this specific interaction should be useful therapeutic agents for a number of significant diseases and conditions including inflammation, heart disease, including myocardial infarction, and tumor metastasis. The present invention includes a chimeric peptide that has high affinity for talin, muteins of talin and integrin &#x3b2;as well as screening methods for agents that can disrupt the interaction between talin and integrin &#x3b2;.

Combined preparation of a thiazide diuretic and a loop diuretic

In a microfluidic system, a magnetic clamp for sealing a flexible microchannel chip includes a base formed from a magnetically-attractable material. The base supports a window for viewing the face of the microfluidic chip. A ring with magnets uniformly distributed around it is disposed over the base. A transparent disk attached to the top of the ring has an inlet and an outlet for introducing and removing a fluid medium into a cavity defined the disk, the window, the center opening of the ring and the base. An elastomer cushion is attached to the inner surface of the disk. The magnetic force between the base and the magnets on the ring compresses the cushion against the microfluidic chip so that the microchannels are sealed against the window with a uniform and reproducible pressure.

Microfluidic system and method for using same

Diagnostic systems, methods, polypeptides and antibodies for detecting the presence of C-terminal hGPIIb fragment of the platelet receptor GPIIb-IIIa in a body fluid sample are disclosed.

Vitro methods for determining in vivo thrombotic events

In vitro methods for determining in vivo thrombotic events

Test kits for detecting the presence of C-terminal hGPIIb fragments

Novel polypeptides derived from human fibronectin are described which bind to integrin receptors expressed by cells. The receptor binding site of human fibronectin begins at amino acid residue,and ends at residue,of fibronectin. The polypeptides facilitate attachment of cells to substrates either alone or in conjunction with RGD-containing peptides. Vectors, fusion proteins and antibodies are also described. Methods for promoting cell attachment and for inhibiting cell adhesion are also described.

Polypeptides for promoting cell attachment

Antibodies for detecting the presence of C-terminal hGPIIb fragment of the platelet receptor GPIIb-IIIa in a body fluid sample are disclosed.

Polypeptides and fusion polypeptides that immunologically mimic the native Pl.sup.A1 and Pl.sup.A2 determinants of platelet protein GPIIIa are disclosed. Also disclosed are DNA segments and recombinant DNA molecules that encode those polypeptides and fusion polypeptides and methods for expressing and using those determinants. Antibodies that immunoreact with one determinant or the other, but not both are also disclosed, as are methods of preparing and using those antibodies.

Platelet GPIII P1.sup.A1 and P1.sup.A2 epitopes, their preparation and

A method for identifying regulators of integrin activation by establishing a selected cell line which contains a functional integrin and a chimeric polypeptide having a cytoplasmic domain of an integrin subunit fused to a polypeptide containing extracellular and transmembrane domains that are not functional integrin domains, so that chimera can inhibit signaling activities of the functional integrin by interaction with integrin regulator molecules in the cytoplasm; transfecting the cell line with a selected cDNA expression library; expressing proteins of the cDNA expression library; and identifying proteins which when overexpressed overcome the inhibition of signaling activities by said chimeric polypeptide, said proteins being regulators of integrin. Methods of designing drugs to modify integrin function and cell lines for screening regulators of integrin activation are also provided.

Methods and cell lines for identification of regulators of integrin

Novel polypeptides derived from human fibronectin are described which bind to integrin receptors expressed by cells. The receptor binding site of human fibronectin begins at amino acid residue 1394 and ends at residue 1400 of fibronectin. The polypeptides facilitate attachment of cells to substrates either alone or in conjunction with RGD-containing peptides. Vectors, fusion proteins and antibodies are also described. Methods for promoting cell attachment and for inhibiting cell adhesion are also described.

.beta..sub.3 integrin subunit specific polypeptides, cDNAs which encode these polypeptides and methods of producing these polypeptides are provided.

.beta.3 integrin subunit specific polypeptides, cDNAS which encode these

Methods are described for characterizing platelet aggregation defects. The defects are characterized as activation, ligand binding, or post-occupancy defects. In one embodiment of the invention a Cam variant of Glanzmann's thrombasthenia is characterized as having a ligand binding defect. In another embodiment, a patient with myelofibrosis is identified as having an activation defect. Rapid analysis are afforded using fluorescence-activated flow cytometry. Also, diagnostic kits are described which comprise antibodies suitable for characterizing the above defects.

Growing community of inventors

San Diego, CA, United States of America

Mark H Ginsberg