pci-32765 and Idiopathic-Pulmonary-Fibrosis

pci-32765 has been researched along with Idiopathic-Pulmonary-Fibrosis* in 2 studies

Other Studies

2 other study(ies) available for pci-32765 and Idiopathic-Pulmonary-Fibrosis

Article	Year
Synthesis and biological activity of thieno[3,2-d]pyrimidines as potent JAK3 inhibitors for the treatment of idiopathic pulmonary fibrosis. Bioorganic & medicinal chemistry, 2020, 01-15, Volume: 28, Issue:2 Idiopathic pulmonary fibrosis (IPF) is a serious and fatal lung disease, with a median survival of only 3-5 years from diagnosis. Janus kinase 3 (JAK3) has a well-established role in the pathogenesis of various autoimmune diseases, including rheumatoid arthritis (RA) and autoimmune-related pulmonary fibrosis. In this study, through the use of a conformationally-constrained design strategy, a series of thieno[3,2-d]pyrimidines were synthesized as potent JAK3 inhibitors for the treatment of IPF. Among them, the most potent JAK3 inhibitor, namely 8e (IC Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Disease Models, Animal; Dose-Response Relationship, Drug; Epithelial Cells; Female; Humans; Idiopathic Pulmonary Fibrosis; Janus Kinase 3; Mice; Mice, Inbred C57BL; Molecular Docking Simulation; Molecular Structure; Protein Kinase Inhibitors; Pyrimidines; Structure-Activity Relationship	2020
Ibrutinib Exacerbates Bleomycin-Induced Pulmonary Fibrosis via Promoting Inflammation. Inflammation, 2018, Volume: 41, Issue:3 Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible lung disease with high mortality rate. The etiology is unknown and treatment choices are limited. Thus, there is great interest to investigate novel agents for IPF therapy. Ibrutinib, BTK, and ITK irreversible inhibitor is a FDA-approved small molecule for the clinical therapy of B cell lymphoma. Its role in pulmonary fibrosis remains unknown. In this study, we investigated the anti-fibrotic activity of ibrutinib. Strikingly, ibrutinib did not inhibit but exacerbated bleomycin-induced pulmonary fibrosis by increased epithelial cell apoptosis, and inflammation in the lung. The upregulated TGF-β and EMT transformation also contributes to enhanced myofibroblast differentiation and ECM deposition. Our findings reveal the detrimental effects of ibrutinib against bleomycin-mediated fibrosis and added to the understanding of IPF pathogenesis. Topics: Adenine; Animals; Apoptosis; Bleomycin; Disease Models, Animal; Epithelial Cells; Humans; Idiopathic Pulmonary Fibrosis; Inflammation; Mice; Piperidines; Pulmonary Fibrosis; Pyrazoles; Pyrimidines	2018

Article

Year

Synthesis and biological activity of thieno[3,2-d]pyrimidines as potent JAK3 inhibitors for the treatment of idiopathic pulmonary fibrosis.

Bioorganic & medicinal chemistry, 2020, 01-15, Volume: 28, Issue:2

Idiopathic pulmonary fibrosis (IPF) is a serious and fatal lung disease, with a median survival of only 3-5 years from diagnosis. Janus kinase 3 (JAK3) has a well-established role in the pathogenesis of various autoimmune diseases, including rheumatoid arthritis (RA) and autoimmune-related pulmonary fibrosis. In this study, through the use of a conformationally-constrained design strategy, a series of thieno[3,2-d]pyrimidines were synthesized as potent JAK3 inhibitors for the treatment of IPF. Among them, the most potent JAK3 inhibitor, namely 8e (IC

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Disease Models, Animal; Dose-Response Relationship, Drug; Epithelial Cells; Female; Humans; Idiopathic Pulmonary Fibrosis; Janus Kinase 3; Mice; Mice, Inbred C57BL; Molecular Docking Simulation; Molecular Structure; Protein Kinase Inhibitors; Pyrimidines; Structure-Activity Relationship

2020

Ibrutinib Exacerbates Bleomycin-Induced Pulmonary Fibrosis via Promoting Inflammation.

Inflammation, 2018, Volume: 41, Issue:3

Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible lung disease with high mortality rate. The etiology is unknown and treatment choices are limited. Thus, there is great interest to investigate novel agents for IPF therapy. Ibrutinib, BTK, and ITK irreversible inhibitor is a FDA-approved small molecule for the clinical therapy of B cell lymphoma. Its role in pulmonary fibrosis remains unknown. In this study, we investigated the anti-fibrotic activity of ibrutinib. Strikingly, ibrutinib did not inhibit but exacerbated bleomycin-induced pulmonary fibrosis by increased epithelial cell apoptosis, and inflammation in the lung. The upregulated TGF-β and EMT transformation also contributes to enhanced myofibroblast differentiation and ECM deposition. Our findings reveal the detrimental effects of ibrutinib against bleomycin-mediated fibrosis and added to the understanding of IPF pathogenesis.

Topics: Adenine; Animals; Apoptosis; Bleomycin; Disease Models, Animal; Epithelial Cells; Humans; Idiopathic Pulmonary Fibrosis; Inflammation; Mice; Piperidines; Pulmonary Fibrosis; Pyrazoles; Pyrimidines

2018