Celltech Therapeutics Limited

Celltech R&d Limited

Ucbbiopharma Srl

John Wyeth Brother, Limited

Ucb Pharma, S.a.

Celltech Limited

Ucb Biopharma Sprl

Graham John Warrellow

John Robert Porter

John Clifford Head

Rikki Peter Alexander

Sarah Catherine Archibald

Ewan C Boyd

Barry John Langham

Timothy John Norman

Janeen Marsha Linsley

Stephen Edward Rapecki

Boris Kroeplien

Alastair Lawson

James Philip O'Connell

Valerie Anne Cole

Michael Anthony Eaton

Brian Woodside Hutchinson

Terence J Ward

Julien Alistair Brown

Andrew James Ratcliffe

William Ross Pitt

James Philip O'CONNELL

Ian A Cliffe

Daniel John Lightwood

Mark Daniel Calmiano

Tracy Lynn Arakaki

Alex Buntin Burgin

David Andreas Schubert

Alan C White

Daniel Christopher Brookings

Andrew Sharpe

Roland W Bürli

James Thomas Reuberson

Christopher Lowe

Verity Margaret Sabin

Daniel Rees Allen

David James McMillan

George Martin Buckley

Richard John Davenport

Rebecca Jayne Munro

Stephen Robert Mack

Marianna Dilani Richard

Christopher James Lock

Mark A Ashwell

Natasha Kinsella

Laura Jane Tait

Emma Louise Trown

Rebecca Jayne Wootton

Sophie Caroline Williams

John Richard Davenport

Roland BÜRLI

David James Mcmillan

A new, stable trimeric TNF&#x3b1; structure is disclosed with distorted symmetry which can bind to the TNFR1 receptor to attenuate signalling therefrom, which can be used in the treatment and/or prevention of diseases associated with the soluble TNF&#x3b1;/TNFR1 interaction. Membrane-bound TNF&#x3b1; is not affected in its ability to signal through TNFR2, and thus the new structure of TNF&#x3b1; may be used in therapies which do not significantly raise the risk of infection or malignancy.

Method of identifying potential inhibitors of APO TNF&#x3b1; trimers

It has been demonstrated that certain compounds bind to TNF and stabilise a conformation of trimeric TNF that binds to the TNF receptor. Accordingly, these compounds can be used as modulators of TNF. A new assay for identifying compounds with this mechanism of action is also disclosed.

Method for identifying a modulator of the TNF&#x3b1; or CD40L interaction with their cognate receptors

The invention is in the field of TNF signalling. Compounds have been identified which are capable of modulating signalling of TNF trimers through receptors. Methods of identifying such compounds are therefore provided. The compounds themselves have utility in therapy.

Methods of identifying signaling modulators of the trimeric TNFa

Treatment of autoimmune and inflammatory disorders with asymmetric TNF alpha trimers

TNF receptor signaling modulator assay

A series of heteroaryl-substituted quinoxaline and quinoline derivatives, being selective inhibitors of PI3 kinase enzymes, are accordingly of benefit in medicine, for example in the treatment of inflammatory, autoimmune, cardiovascular, neurodegenerative, metabolic, oncological, nociceptive or ophthalmic conditions, said substituted derivatives having the general formula 

Quinoxaline and quinoline derivatives as kinase inhibitors

Alkanoic acid derivatives of formula (1) are described:Ar(Alk)LArCH(R)C(R)(R)R&#x2003;&#x2003;(1) The compounds are able to inhibit the binding of &#x3b1;4 integrins to their ligands and are of use in the prophylaxis and treatment of immune or inflammatory disorders.

&#x3b2;-alanine derivates

Phenylalanine derivatives of formula (1) are described:wherein The compounds are able to inhibit the binding of a 4 integrins to their ligands and are of use in the prophylaxis and treatment of diseases or disorders involving inflammation.

Growing community of inventors

Northwood, United Kingdom

Graham John Warrellow