The University of Queensland

University of Nebraska

Promics Pty Limited

Stephen Maxwell Taylor

David P Fairlie

Sam D Sanderson

Leonid Kirnarsky

Simon A Sherman

Ian Alexander Shiels

Michael Wellesley Whitehouse

Allan Wong

Angela Monique Finch

Darren Ray March

Trent Martin Woodruff

Lindsay Charles Brown

David Fairlie

This invention relates to the use of an antagonist of a G protein-coupled receptor in the prevention and/or treatment of fibrosis, such as the treatment of fibrosis associated with myocardial infarction or diabetes or certain pulmonary conditions. In a preferred embodiment, the antagonist is a C5a receptor antagonist, more preferably a cyclic peptide antagonist of the C5a receptor. In particular, the invention provides a method of prevention, treatment or alleviation of a fibrotic condition, comprising the step of administering an effective amount of an antagonist of a G protein-coupled receptor to a subject in need of such treatment.

Use of C5a receptor antagonist in the treatment of fibrosis

The present invention relates to novel cyclic or constrained acyclic compounds which modulate the activity of G protein-coupled receptors and are useful in the treatment of conditions mediated by G protein-coupled receptors, for example, inflammatory conditions.

Cyclic agonists and antagonists of C5A receptors and G Protein-coupled receptors

The invention relates to novel cyclic compounds which have the ability to modulate the activity of G protein-coupled receptors. The compounds preferably act as antagonists. In preferred embodiments, the invention provides cyclic peptidic and peptidomimetic antagonists of C5a receptors, which are active against C5a receptors on polymorphonuclear leukocytes and macrophages. The compounds of the invention are both potent and selective, and are useful in the treatment of a variety of inflammatory conditions.

Cyclic peptides as G-protein-coupled receptor antagonists

This invention relates to methods of treatment of inflammatory bowel disease, and especially to treatment of this condition with cyclic peptidic and peptidomimetic compounds which have the ability to modulate the activity of G protein-coupled receptors. The compounds preferably act as antagonists of the C5a receptor, and are active against C5a receptors on polymorphonuclear leukocytes and macrophages. Particularly preferred compounds for use in the methods of the invention are disclosed.

Treatment of inflammatory bowel disease

Cyclic agonists and antagonists of C5a receptors and G protein-coupled receptors

High-affinity response-selective C-terminal analogs of C5 anaphylatoxin are provided. Whereas natural C5 has considerable flexibility in the C-terminal region, the analogs of the invention possess a backbone conformation which is constrained at the C-terminus to a &bgr;-turn. The stabilized &bgr;-turn confers a marked increase in potency of the analogs; the particular &bgr;-turn motif further confers the capability to selectively elicit certain biological responses associated with C5 . Exemplary compounds of the invention are decapeptide analogs of the formula: A1-Ser-Phe-Lys-A2-A3-A4-A5-A6-A7, with the constrained &bgr;-turn being localized in the region of A4-A7.

High-affinity response-selective C-terminal analogs of C5a anaphylatoxin

High-affinity response-selective C-terminal analogs of C5a anaphylatoxin are provided. Whereas natural C5a has considerable flexibility in the C-terminal region, the analogs of the invention possess a backbone conformation which is constrained at the C-terminus to a .beta.-turn. The stabilized .beta.-turn confers a marked increase in in potency of the analogs; the particular .beta.-turn motif further confers the capability to selectively elicit certain biological responses associated with C5a. Exemplary compounds of the invention are decapeptide analogs of the formula: A1-Ser-Phe-Lys-A2-A3-A4-A5-A6-A7, with the constrained .beta.-turn being localized in the region of A4-A7.

Growing community of inventors

Bellbird Park, Australia

Stephen Maxwell Taylor