title: Chemical biology tools for regulating RAS signaling complexity in space and time.
abstract: Rat sarcoma (RAS) family members are small GTPases that control a number of signaling pathways important for normal cellular proliferation. Therefore, it is no surprise that a significant portion of human tumors express constitutively active mutated RAS proteins, which leads to deregulation of RAS signaling pathways, resulting in pathological perturbations of cell growth and death. Although the molecular details of RAS signaling cascades are well understood, there is still a largely unmet need for small molecule probes to control RAS signaling in space and time. More broadly, given the prevalence of mutated RAS in cancer, the need to translate the insights obtained from using small molecule probes into clinically useful drugs is also significant. In this review, we introduce RAS proteins and the signaling pathways they are involved in, and discuss some of the innovative chemical biology approaches to regulate RAS signaling, which include the exploitation of newly identified binding pockets, covalent inhibitors for mutated RAS, and RAS localization impairment.
authors.affiliation: Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany.
authors.forename: Hilde
authors.initials: H
authors.lastname: van Hattum
authors.affiliation: Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany; Department of Chemistry and Chemical Biology, TU Dortmund, Otto-Hahn-Strasse 6, 44227 Dortmund, Germany. Electronic address: herbert.waldmann@mpi-dortmund.mpg.de.
authors.forename: Herbert
authors.initials: H
authors.lastname: Waldmann
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D008745:Methylation; D017368:Protein Prenylation; D015398:Signal Transduction; D054852:Small Molecule Libraries / Q000737:chemistry / Q000378:metabolism; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D054852:Small Molecule Libraries; D018631:ras Proteins