title: The effect of RO3201195 and a pyrazolyl ketone P38 MAPK inhibitor library on the proliferation of Werner syndrome cells.
abstract: Microwave-assisted synthesis of the pyrazolyl ketone p38 MAPK inhibitor RO3201195 in 7 steps and 15% overall yield, and the comparison of its effect upon the proliferation of Werner Syndrome cells with a library of pyrazolyl ketones, strengthens the evidence that p38 MAPK inhibition plays a critical role in modulating premature cellular senescence in this progeroid syndrome and the reversal of accelerated ageing observed in vitro on treatment with SB203580.
authors.affiliation: Department of Chemistry, School of Life Sciences, University of Sussex, Falmer, Brighton, East Sussex, BN1 9QJ, UK. m.c.bagley@sussex.ac.uk.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Bagley
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Dwyer
authors.forename: Mohammed
authors.initials: M
authors.lastname: Baashen
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Dix
authors.forename: Paola G S
authors.initials: PG
authors.lastname: Murziani
authors.forename: Michal J
authors.initials: MJ
authors.lastname: Rokicki
authors.forename: David
authors.initials: D
authors.lastname: Kipling
authors.forename: Terence
authors.initials: T
authors.lastname: Davis
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008872:Microwaves; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014898:Werner Syndrome / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C509704:5-amino-1-(4-fluorophenyl)-4-(3-(2,3-dihydroxypropoxy)benzoyl)pyrazole; D007659:Ketones; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D054852:Small Molecule Libraries; D048051:p38 Mitogen-Activated Protein Kinases