Benzothiophene inhibitors of MK2. Part 1: structure-activity relationships, assessments of selectivity and cellular potency.
Identification of potent benzothiophene inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK2), structure-activity relationship (SAR) studies, selectivity assessments against CDK2, cellular potency and mechanism of action are presented. Crystallographic data provide a rationale for the observed MK2 potency as well as selectivity over CDK2 for this class of inhibitors.
Anderson
David R
DR
Pfizer Global Research and Development, St Louis Laboratories, Chesterfield, MO 63017, USA. david.r.anderson@pfizer.com
Meyers
Marvin J
MJ
Kurumbail
Ravi G
RG
Caspers
Nicole
N
Poda
Gennadiy I
GI
Long
Scott A
SA
Pierce
Betsy S
BS
Mahoney
Matthew W
MW
Mourey
Robert J
RJ
D001665:Binding Sites; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D048370:MAP Kinase Kinase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D047428:Protein Kinase Inhibitors; D013876:Thiophenes; C088015:benzothiophene; D051357:Cyclin-Dependent Kinase 2; D048370:MAP Kinase Kinase 2