title: VX-745. Vertex Pharmaceuticals.
abstract: VX-745, a lead anti-inflammatory candidate, small-molecule inhibitor of mitogen-activated protein kinase (MAPK), is under development by Vertex Pharmaceuticals Inc in association with Kissei Pharmaceutical Co Ltd for the potential treatment of rheumatoid arthritis (RA) [214928]. VX-745 was introduced by Vertex as a potential antiinflammatory drug for the treatment of RA in a pilot phase II trial initiated in November 1999 [346067]. In June 2000, phase II trials were still ongoing [371819] and in January 2001, Vertex initiated a randomized, double-blind, placebo-controlled phase II trial in adult patients with RA, with the objective of evaluating clinical response rates, self-reported patient health assessments and pharmacodynamic markers of drug activity [395083]. During the 33rd Annual Meeting of the American Chemical Society in May 2000, VX-745 was reported to be active against several isotypes of p38 MAPK, including p38alpha, p38beta and p38gamma [368149]. The targeting of p38 MAPK by VX-745 was associated with the suppression of the release of inflammatory mediators, including interleukin (IL)-1beta and tumor necrosis factor (TNF)alpha, known to be implicated in exacerbating the pathophysiology of RA [273648], [368149], [371548], [372054], [408713].
authors.affiliation: Tayside Institute of Child Health, Faculty of Medicine, Dentistry & Nursing, Ninewells Hospital and Medical School, University of Dundee, Scotland, UK. j.j.haddad@dundee.ac.uk
authors.forename: J J
authors.initials: JJ
authors.lastname: Haddad
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D011724:Pyridazines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D011724:Pyridazines; D011743:Pyrimidines; D020928:Mitogen-Activated Protein Kinases; C464966:VX-745