University of Dundee

Centre National De La Recherche Scientifique

Dana-farber-cancer Institute Inc.

Zeneca Limited

University Court of the University of Dundee

Novartis Ag

Medical Research Council

Université Blaise Pascal - Clermont-ferrand II

Medical Research Council London

Philip Cohen

Nathanael Schiander Gray

Hwan Geun Choi

George R Brown

Dearg Sutherland Brown

Dario Alessi

Kristopher Clark

Laurent Meijer

Brian Arthur Hemmings

Mirjana Andjelkovic

Peter Gregory Goekjian

Amaury Patin

Michelle Prudhomme

Fabrice Anizon

Pascale Moreau

Michel Goedert

Patricia Townsend Wade Cohen

Chris Armstrong

Philippe Olivier Belmont

David Barford

Maria Deak

Takayasu Kobayashi

Matilde Caivano

Marin Deak

Darren Cross

Peter David Cron

Johann Bosson

Emilie Rossignol

Rufine Akue-Gedu

Bettina Aboab

The present invention relates to the discovery that salt inducible kinases (SIKs) suppress the formation of anti-inflammatory molecules such as IL-10, which are important for the resolution of inflammation and identifies SIK inhibitors that may be used to treat disorders associated with undesirable inflammation, such as inflammatory bowel disease and/or autoimmune disorders.

SIK inhibitor for use in a method of treating an inflammatory and/or immune disorder

The invention relates to kinase inhibitors of the formula (I) in which &#x2014;Rto R&#x2550;H; ether or polyether, amino; NO; NH-carbamate; NH&#x2014;CO&#x2014;R, with R such as defined above; Nand derivatives thereof of the 1,2,3-triazole type; &#x2014;R=&#x2014;OH; halogen; &#x2014;OR with R such as defined above; OH-carbamate; OH-carbonate; NH, NH-carbamate; NH&#x2014;CO&#x2014;R, with R such as defined above; Nand derivatives thereof of the 1,2,3-triazole type; N(R,R); &#x2014;R'&#x2550;H or a C1-C12 alkyl, &#x2014;R&#x2550;H; R; (R or R&#x2032;)&#x2014;Si, with R such as defined above; optionally substituted aryl, heteroaryl; halogen (iodine); alkynyl; &#x2014;Rand R&#x2550;H, C-Calkyl; &#x2014;Rand R&#x2550;H, R (or R&#x2032;) such as defined above. These compounds can be used as kinase inhibitors in particular for treating cancer.

Tetrahydrocyclopenta[c]acridine derivatives as kinase inhibitors and biological

The invention relates to pyrrolo[2,3-a]carbazole derivatives, to a method for preparing the same, and to the use thereof as PIM kinase inhibitors. The invention can particularly be used in the pharmaceutical field.

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The invention concerns RAC-PK and fragments thereof, as well as activators and inhibitors of RAC-PK for use as medicaments, particularly in the treatment of diseases concerned with abnormalities in processes modulated by insulin, such as cellular proliferation, insulin deficiency and/or excess blood sugar levels. Moreover, the invention provides RAC-PK for use in screening potential mimics or modulators thereof. A method for screening for agents capable of affecting the activity of GSK3 is also disclosed. The invention further provides a screening kit comprising the RAC-PK as an active principle, and a method for screening compounds which are candidate mimics or modulators of RAC-PK activity comprising detecting specific interactions between the candidate compounds and RAC-PK. There is also provided a process for activating RAC-PK comprising treatment thereof with a phosphatase inhibitor.

Activation of mutated RAC-PK

A kit of parts comprising two or more protein kinase substrate polypeptides, each said substrate polypeptide comprising a specificity conferring portion (which is different for each said kinase substrate polypeptide) and a phosphorylatable portion, wherein the phosphorylatable portions of each polypeptide are capable of being bound in a phosphorylation state-sensitive manner by the same specific binding partner, for example and antibody preparation, and wherein the said specific binding partner is not an antibody specific for phosphotyrosine, phosphoserine or phosphothreonine. The phosphorylatable portion preferably comprises the amino acid sequence LSFAEPG.

Methods and reagents for assaying protein kinase activity

Substantially pure two kinase domain protein kinases comprising the amino acid sequences provided in the description, variants, fusions, fragments, or derivatives thereof useful in screening assays for drugs. Applications thereof in the modulation of CREB, COX2 and IL2 activities.

Polypeptides, polynucleotides and uses thereof

A method of activating serum and glucocorticoid-induced protein kinase (SGK) is provided wherein the SGK is phosphorylated. The SGK may be phosphorylated by PDK1 and/or a preparation containing PDK2 activity. A method of identifying a compound that modulates the activity of SGK is provided, wherein the activity of SGK is measured by measuring the phosphorylation by SGK of a polypeptide comprising an amino acid sequence corresponding to the consensus sequence (Arg/Lys; preferably Arg)-X-(X/Arg)-X-X-Ser/Thr)-Z wherein X indicates any amino acid, X/Arg indicates any amino acid, with a preference for arginine, and Z indicates that the amino acid residue is preferably a hydrophobic residue. The SGK may be activated by phosphorylation.

Methods

A method of identifying a compound which modulates the interaction between a PP1c and a regulatory subunit thereof, the method comprising determining whether a compound enhances or disrupts the interaction between (a) a PP1c or a fragment, variant, derivative or fusion thereof or a fusion of a fragment, variant or derivative and (b) a regulatory subunit which is able to bind to PP1c or a PP1c-binding fragment, variant, derivative or fusion of the subunit or a fusion of the fragment, variant or derivative. A method of affecting cellular metabolism or function, the method comprising administering to a cell (a) a compound which modulates the interaction between a PP1c and a regulatory subunit thereof or (b) a compound which mimics the effect of a regulatory subunit of PP1c or (c) a peptide capable of binding a PP1c and which affects the ability of PP1c to bind to a particular target and/or affects the regulation of PP1c activity, or a functional equivalent thereof.

Protein phosphatase-1 catalytic subunit interactions

The invention concerns the use of amide derivatives of formula (I) wherein: R and R are substituents such as hydroxy, C alkoxy, mercapto, C alkylthio, amino, C alkylamino and di-(C alkyl)amino; m and p are independently 0-3; R is C alkyl; q is 0-4; and R is aryl or cycloalkyl; or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for use in the treatment of diseases or medical conditions mediated by cytokines

Amide derivatives for the treatment of diseases mediated by cytokines

The present invention relates to a method of identifying a compound which blocks the activation of a stress-activated protein kinase selected from the group consisting of SAPK4 and SAPK3 by SKK3. The method includes contacting the stress-activated protein kinase with the compound and determining whether the compound enhances or disrupts the interaction between the stress-activated protein kinase and SKK3. The invention further relates to a screening assay, a method of identifying agents able to influence the activity of a stress-activated protein kinase and a method of activating a stress-activated protein kinase.

MAP kinases: polypeptides, polynucleotides and uses thereof

The invention concerns the use of amide derivatives of formula (I) wherein: R and R are substituents such as hydroxy, C alkoxy, mercapto, C alkylthio, amino, C alkylamino and di-(C alkyl)amino; m and p are independently 0-3R is C alkyl; q is 0-4; and R is aryl or cycloalkyl; or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for use in the treatment of diseases or medical conditions mediated by cytokines

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Dundee, United Kingdom

Philip Cohen