title: Latest Advances Towards Ras Inhibition: A Medicinal Chemistry Perspective.
abstract: Owing to their high occurrence rate across many human cancers and their lack of druggability so far, mutant forms of the signaling protein Ras are currently among the most attractive (and elusive) oncology targets. This strong appeal explains the sustained effort in the field, and the ensuing progress has rekindled optimism regarding the discovery of Ras inhibitors. In this Minireview, we discuss the most recent advances towards irreversible inhibitors, and highlight approaches to inhibitors of Ras-effector interactions that have been overshadowed by the current focus on direct Ras inhibition. At the same time, we provide a critical assessment from a medicinal chemistry perspective.
authors.affiliation: Bayer Pharma AG, Drug Discovery, Medicinal Chemistry Berlin, Muellerstrasse 178, 13353, Berlin, Germany.
authors.forename: Brice
authors.identifier: 0000-0003-3854-7629
authors.initials: B
authors.lastname: Sautier
authors.affiliation: Bayer Pharma AG, Drug Discovery, Medicinal Chemistry Berlin, Muellerstrasse 178, 13353, Berlin, Germany.
authors.forename: Carl F
authors.initials: CF
authors.lastname: Nising
authors.affiliation: Bayer Pharma AG, Drug Discovery, Medicinal Chemistry Berlin, Muellerstrasse 178, 13353, Berlin, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Wortmann
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D018631:ras Proteins / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D018631:ras Proteins
keywords: Ras; computational chemistry; inhibitors; medicinal chemistry; peptides