pf-03491390 has been researched along with Liver-Diseases* in 2 studies
2 other study(ies) available for pf-03491390 and Liver-Diseases
| Article | Year |
|---|---|
Structure-activity relationship study of a series of caspase inhibitors containing γ-amino acid moiety for treatment of cholestatic liver disease.
A series of caspase inhibitors containing γ-amino acid moiety have been synthesized. A systemic study on their structure-activity relationship of anti-apoptotic cellular activity is presented. These efforts led to the discovery of compound 20o as a potent caspase inhibitor, which demonstrated preclinical ameliorating total bilirubin efficacy with a significantly improved pharmacokinetic profile. Topics: Amino Acids; Animals; Bilirubin; Binding Sites; Caspase 1; Caspase Inhibitors; Disease Models, Animal; fas Receptor; Half-Life; Humans; Jurkat Cells; Liver Diseases; Mice; Molecular Docking Simulation; Protein Structure, Tertiary; Structure-Activity Relationship | 2018 |
First-in-class pan caspase inhibitor developed for the treatment of liver disease.
A series of oxamyl dipeptides were optimized for pan caspase inhibition, anti-apoptotic cellular activity and in vivo efficacy. This structure-activity relationship study focused on the P4 oxamides and warhead moieties. Primarily on the basis of in vitro data, inhibitors were selected for study in a murine model of alpha-Fas-induced liver injury. IDN-6556 (1) was further profiled in additional in vivo models and pharmacokinetic studies. This first-in-class caspase inhibitor is now the subject of two Phase II clinical trials, evaluating its safety and efficacy for use in liver disease. Topics: Adult; Alanine Transaminase; Animals; Apoptosis; Aspartate Aminotransferases; Biological Availability; Caspase 3; Caspase Inhibitors; Cholestasis; Clinical Trials, Phase I as Topic; Half-Life; Hepatitis C, Chronic; Hepatocytes; Humans; Jurkat Cells; Liver; Liver Diseases; Mice; Pentanoic Acids; Rats; Structure-Activity Relationship | 2005 |