Benzothiophene inhibitors of MK2. Part 2: improvements in kinase selectivity and cell potency.
Optimization of kinase selectivity for a set of benzothiophene MK2 inhibitors provided analogs with potencies of less than 500 nM in a cell based assay. The selectivity of the inhibitors can be rationalized by examination of X-ray crystal structures of inhibitors bound to MK2.
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
Parikh
Mihir D
MD
D001665:Binding Sites; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D048370:MAP Kinase Kinase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; 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