title: Discovery of Dinaciclib (SCH 727965): A Potent and Selective Inhibitor of Cyclin-Dependent Kinases.
abstract: Inhibition of cyclin-dependent kinases (CDKs) has emerged as an attractive strategy for the development of novel oncology therapeutics. Herein is described the utilization of an in vivo screening approach with integrated efficacy and tolerability parameters to identify candidate CDK inhibitors with a suitable balance of activity and tolerability. This approach has resulted in the identification of SCH 727965, a potent and selective CDK inhibitor that is currently undergoing clinical evaluation.
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Kamil
authors.initials: K
authors.lastname: Paruch
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Dwyer
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Carmen
authors.initials: C
authors.lastname: Alvarez
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Courtney
authors.initials: C
authors.lastname: Brown
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Tin-Yau
authors.initials: TY
authors.lastname: Chan
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Doll
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Kerry
authors.initials: K
authors.lastname: Keertikar
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Chad
authors.initials: C
authors.lastname: Knutson
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Brian
authors.initials: B
authors.lastname: McKittrick
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Rivera
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Randall
authors.initials: R
authors.lastname: Rossman
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Greg
authors.initials: G
authors.lastname: Tucker
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Thierry
authors.initials: T
authors.lastname: Fischmann
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Alan
authors.initials: A
authors.lastname: Hruza
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Vincent
authors.initials: V
authors.lastname: Madison
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Amin A
authors.initials: AA
authors.lastname: Nomeir
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Yaolin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Paul
authors.initials: P
authors.lastname: Kirschmeier
authors.affiliation: Merck Research Laboratories, 901 California Avenue, Palo Alto, California 94304.
authors.forename: Emma
authors.initials: E
authors.lastname: Lees
authors.affiliation: Merck Research Laboratories, 901 California Avenue, Palo Alto, California 94304.
authors.forename: David
authors.initials: D
authors.lastname: Parry
authors.affiliation: Merck Research Laboratories, 901 California Avenue, Palo Alto, California 94304.
authors.forename: Nicole
authors.initials: N
authors.lastname: Sgambellone
authors.affiliation: Merck Research Laboratories, 901 California Avenue, Palo Alto, California 94304.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Seghezzi
authors.affiliation: Merck Research Laboratories, 901 California Avenue, Palo Alto, California 94304.
authors.forename: Lesley
authors.initials: L
authors.lastname: Schultz
authors.affiliation: Merck Research Laboratories, 901 California Avenue, Palo Alto, California 94304.
authors.forename: Frances
authors.initials: F
authors.lastname: Shanahan
authors.affiliation: Merck Research Laboratories, 901 California Avenue, Palo Alto, California 94304.
authors.forename: Derek
authors.initials: D
authors.lastname: Wiswell
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Xu
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Quiao
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Ligand Pharmaceuticals (formerly Pharmacopeia), 3000 Eastpark Boulevard, Cranbury, New Jersey 08512.
authors.forename: Ray A
authors.initials: RA
authors.lastname: James
authors.affiliation: Ligand Pharmaceuticals (formerly Pharmacopeia), 3000 Eastpark Boulevard, Cranbury, New Jersey 08512.
authors.forename: Vidyadhar M
authors.initials: VM
authors.lastname: Paradkar
authors.affiliation: Ligand Pharmaceuticals (formerly Pharmacopeia), 3000 Eastpark Boulevard, Cranbury, New Jersey 08512.
authors.forename: Haengsoon
authors.initials: H
authors.lastname: Park
authors.affiliation: Ligand Pharmaceuticals (formerly Pharmacopeia), 3000 Eastpark Boulevard, Cranbury, New Jersey 08512.
authors.forename: Laura R
authors.initials: LR
authors.lastname: Rokosz
authors.affiliation: Ligand Pharmaceuticals (formerly Pharmacopeia), 3000 Eastpark Boulevard, Cranbury, New Jersey 08512.
authors.forename: Tara M
authors.initials: TM
authors.lastname: Stauffer
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Guzi
keywords: Cyclin-dependent kinase; SCH 727965; oncology therapeutics