title: Drugs by numbers: reaction-driven de novo design of potent and selective anticancer leads.
abstract: A potent and selective inhibitor of the anticancer target Polo-like kinase 1 was found by computer-based molecular design. This type II kinase inhibitor was synthesized as suggested by the design software DOGS and exhibited significant antiproliferative effects against HeLa cells without affecting nontransformed cells. The study provides a proof-of-concept for reaction-based de novo design as a leading tool for drug discovery.
authors.affiliation: Universitätsfrauenklinik, Molekulare Onkologie und Gynäkologie, Eberhard Karls Universität, Calwerstrasse 7, 72076 Tübingen, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Spänkuch
authors.forename: Sarah
authors.initials: S
authors.lastname: Keppner
authors.forename: Lisa
authors.initials: L
authors.lastname: Lange
authors.forename: Tiago
authors.initials: T
authors.lastname: Rodrigues
authors.forename: Heiko
authors.initials: H
authors.lastname: Zettl
authors.forename: Christian P
authors.initials: CP
authors.lastname: Koch
authors.forename: Michael
authors.initials: M
authors.lastname: Reutlinger
authors.forename: Markus
authors.initials: M
authors.lastname: Hartenfeller
authors.forename: Petra
authors.initials: P
authors.lastname: Schneider
authors.forename: Gisbert
authors.initials: G
authors.lastname: Schneider
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015195:Drug Design; D006367:HeLa Cells; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D000097869:Polo-Like Kinase 1
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1