title: A Carbohydrate-Derived Splice Modulator.
abstract: Small-molecule splice modulators have recently been recognized for their clinical potential for diverse cancers. This, combined with their use as tools to study the importance of splice-regulated events and their association with disease, continues to fuel the discovery of new splice modulators. One of the key challenges found in the current class of materials arises from their instability, where rapid metabolic degradation can lead to off-target responses. We now describe the preparation of bench-stable splice modulators by adapting carbohydrate motifs as a central scaffold to provide rapid access to potent splice modulators.
authors.affiliation: Department of Chemistry and Biochemistry, University of California-San Diego , 9500 Gilman Drive, La Jolla, California 92093-0358, United States.
authors.forename: Sachin
authors.initials: S
authors.lastname: Dhar
authors.affiliation: Department of Chemistry and Biochemistry, University of California-San Diego , 9500 Gilman Drive, La Jolla, California 92093-0358, United States.
authors.forename: James J
authors.initials: JJ
authors.lastname: La Clair
authors.affiliation: Department of Chemistry and Biochemistry, University of California-San Diego , 9500 Gilman Drive, La Jolla, California 92093-0358, United States.
authors.forename: Brian
authors.initials: B
authors.lastname: León
authors.affiliation: Department of Chemistry and Biochemistry, University of California-San Diego , 9500 Gilman Drive, La Jolla, California 92093-0358, United States.
authors.forename: Justin C
authors.initials: JC
authors.lastname: Hammons
authors.affiliation: Moores Cancer Center, University of California-San Diego , La Jolla, California 92093-0358, United States.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Moores Cancer Center, University of California-San Diego , La Jolla, California 92093-0358, United States.
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Kashyap
authors.affiliation: Moores Cancer Center, University of California-San Diego , La Jolla, California 92093-0358, United States.
authors.forename: Januario E
authors.initials: JE
authors.lastname: Castro
authors.affiliation: Department of Chemistry and Biochemistry, University of California-San Diego , 9500 Gilman Drive, La Jolla, California 92093-0358, United States.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Burkart
mesh_terms: D017398:Alternative Splicing / Q000187:drug effects; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D002241:Carbohydrates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004852:Epoxy Compounds / Q000737:chemistry / Q000494:pharmacology; D005233:Fatty Alcohols / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy; D018942:Macrolides / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D011714:Pyrans / Q000737:chemistry / Q000494:pharmacology; D017381:Spliceosomes / Q000737:chemistry* / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D002241:Carbohydrates; D004852:Epoxy Compounds; C091810:FD 895; D005233:Fatty Alcohols; D018942:Macrolides; D011714:Pyrans; C522342:pladienolide B; C076087:herboxidiene