Intermune, Inc.

Other

Leland Stanford Junior University

Karl Kossen

Leonid Beigelman

Scott D Seiwert

Vladimir Serebryany

Donald Ruhrmund

Lawrence M Blatt

Ramachandran Radhakrishnan

Tao Hu

Luca Francesco Mario Raveglia

Stefania Vallese

Ivana Bianchi

Alan J Cohen

Luca Francesco Raveglia

Mark R Nicolls

Xiaoli Qin

Sharlene R Lim

Scott S Seiwert

Disclosed are compounds and methods for treating inflammatory and fibrotic disorders, including methods of modulating a stress activated protein kinase (SAPK) system with an active compound, wherein the active compound exhibits low potency for inhibition of the p38 MAPK; and wherein the contacting is conducted at a SAPK-modulating concentration that is at a low percentage inhibitory concentration for inhibition of the p38 MAPK by the compound. Also disclosed are derivatives and analogs of pirfenidone, useful for modulating a stress activated protein kinase (SAPK) system. Mederski et al., Tetrahedron (1999), 55(44), 12757-12770.* Azuma et al., 'A placebo control and double blind phase II clinical study of pirfenidone in patients with idiopathic pulmonary fibrosis in Japan', Am J Respir Crit Care Med., 165:A729 (2002). Badger, et al., 'Pharmacological profile of SB 203580, a selective inhibitor of cytokine suppressive binding protein/p38 kinase, in animal models of arthritis, bone resorption, endotoxin shock and immune function', J. Pharmacol. Exp. Ther. 279:1453-61 (1996).

Compounds and methods for treating inflammatory and fibrotic disorders

Disclosed are methods of modulating a stress activated protein kinase (SAPK) system with an active compound, wherein the active compound exhibits low potency for inhibition of at least one p38 MAPK; and wherein the contacting is conducted at a SAPK-modulating concentration that is at a low percentage inhibitory concentration for inhibition of the at least one p38 MAPK by the compound. Also disclosed are derivatives of pirfenidone. These derivatives can modulate a stress activated protein kinase (SAPK) system.

Method of modulating stress-activated protein kinase system

Provided herein are novel biomarkers for the identification, prediction or monitoring of fibrotic pulmonary diseases (e.g. idiopathic pulmonary fibrosis (IPF)). The biomarkers provided herein may further be used for therapeutic treatment of IPF.

Proteomic IPF markers

The disclosure relates to methods of preserving or improving microvascular integrity in a patient in need thereof comprising administering pirfenidone therapy to the patient.

Methods of improving microvascular integrity

Disclosed are compounds and methods for treating inflammatory and fibrotic disorders, including methods of modulating a stress activated protein kinase (SAPK) system with an active compound, wherein the active compound exhibits low potency for inhibition of the p38 MAPK; and wherein the contacting is conducted at a SAPK-modulating concentration that is at a low percentage inhibitory concentration for inhibition of the p38 MAPK by the compound. Also disclosed are derivatives and analogs of pirfenidone, useful for modulating a stress activated protein kinase (SAPK) system.

Growing community of inventors

Brisbane, CA, United States of America

Karl Kossen