title: Remediating cancer via splicing modulation.
abstract: The identification of three distinct but structurally related classes of microbial-derived spliceosome modulators has provided an exciting opportunity for the development of mechanistically new cancer treatments. A team at UC San Diego has undertaken a SAR study on the spliceosome modulator FD-895 that focused on improving compound stability, while retaining potent antiproliferative and splicing activity. This led to the identification of a more potent and stable analog, (17S)-FD-895 (1), and a less active but extremely stable cyclopropane analog 2, which is currently undergoing preclinical evaluation. These analogs will serve as templates for next generation spliceosome modulating anticancer drugs.
authors: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland , St. Lucia, Brisbane, 4072, Australia.
authors: Mark S
authors: MS
authors: Butler
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D012326:RNA Splicing / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents