Max-Planck-Gesellschaft Zur F&#xf6;rderung Der Wissenschaften E. V.

Other

The Salk Institute for Biological Studies

Beth Israel Deaconess Medical Center, Inc.

Lead Discovery Center Gmbh

Gunter Fischer

Kun Ping Lu

Michael I Bukrinsky

Miroslav Malesevic

Frank Erdmann

Stephanie Constant

Joseph Noel

Lewis C Cantley

Gerd Ruhter

Michael B Yaffe

Peter Nussbaumer

Gerd Rühter

Jan Kühling

Mark A Verdecia

Klaus Dinkel

Robert K Suto

Janusz M Sowadski

Cordelia Schiene-Fischer

Judith Maria Habazettl

Gerhard Küllertz

The present invention relates to novel cyclosporin derivatives that do not cross the cellular membrane. The compounds according to the invention are used in medicine, more particularly in the treatment/diagnosis of acute and chronic inflammatory diseases, viral infections, cancer, degenerative muscle diseases, neurodegenerative diseases and damage that is associated with calcium homeostasis impairment. The novel cyclosporin derivatives additionally have no immunosuppressive effect.

Cyclosporin derivatives

A cyclosporin derivative of general Formula (I) or a pharmaceutically compatible salt thereof, which have a pharmaceutical effectiveness, for example in the case of chronic inflammatory diseases. The cyclosporin derivatives are preferably free from a peptide section capable of passing through the membrane of a biological cell.

The invention is directed to peptide modulators of Pin1 and Pin1-related proteins and the use of such modulators for treatment of Pin1 associated states, e.g., for the treatment of cancer or neurodegenerative disease.

Pin1-modulating compounds and methods of use thereof

The present invention is based on the finding that the cis/trans isomerisation of secondary amide peptide bonds in oligo- and polypeptides can be catalytically promoted. This catalysis is effected by enzymes which are hereinafter called 'secondary amide peptide bond cis/trans isomerases (APIases). It can be assumed that the APIase activity plays a central role in a number of pathophysiological processes. Thus, the invention relates to pharmaceutical compositions comprising substances which inhibit APIase activity.

Catalysis of the cis/trans-isomerisation of secondary amide peptide compounds

Inhibitors of phosphoserine- or posphothreonine-specific peptidyl prolyl isomerases are described. Such inhibitors include molecules that mimic the structure and conformation of the pSer/pThr-Pro peptide moiety of the isomerase substrate when the substrate is bound into the active site of the isomerase. For example, a protein, peptide or peptide mimetic including xSer/ThrY where x is a negatively charged tetra or pentavalent moiety and Y is a Pro or a Pro analog. Methods of inhibiting cell growth and methods of identifying phosphoserine- or phosphothreonine-proline specific peptidyl-prolyl isomerase inhibitors are also included in the invention.

Inhibitors of phosphoserine and phosphothreonine-proline-specific isomerases

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Halle, Germany

Gunter Fischer