Diene Substitution Patterns in the Conformation-Activity Relationships of GEX1A.

Christian A Umaña, Matthew C Rhodes, Jeffrey L Henry, Duoming Ma, Taylor R Quinn, Richard E Taylor

Abstract read

In one paragraph

Article in ChemMedChem, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Christian A UmañaDepartment of Chemistry and Biochemistry and the Warren Center for Drug Discovery, University of Notre Dame, Notre Dame, Indiana, USA.

Matthew C RhodesDepartment of Chemistry and Biochemistry and the Warren Center for Drug Discovery, University of Notre Dame, Notre Dame, Indiana, USA.

Jeffrey L HenryDepartment of Chemistry and Biochemistry and the Warren Center for Drug Discovery, University of Notre Dame, Notre Dame, Indiana, USA.

Duoming MaDepartment of Chemistry and Biochemistry and the Warren Center for Drug Discovery, University of Notre Dame, Notre Dame, Indiana, USA.

Taylor R QuinnDepartment of Chemistry and Biochemistry and the Warren Center for Drug Discovery, University of Notre Dame, Notre Dame, Indiana, USA.

Richard E TaylorDepartment of Chemistry and Biochemistry and the Warren Center for Drug Discovery, University of Notre Dame, Notre Dame, Indiana, USA.

Funding

Chemistry-Biochemistry-Biology Training Program at Notre DameT32GM075762 · NIGMS · UNIVERSITY OF NOTRE DAME · PI CHANG, MAYLAND F, MOBASHERY, SHAHRIAR · 2007 to 2021

$3.7M

NIH HHS GM147637NIH HHS T32GM075762

6 · The paper itself

Abstract

GEX1A (herboxidiene) is a polyketide natural product that possesses potent biological activities for a number of indications. GEX1A binds the splicing factor 3B subunit 1 (SF3B1), inhibiting the splicing of pre-mRNA. Moreover, we have reported that GEX1A reverses cholesterol accumulation in Niemann-Pick Type C mutant fibroblasts. Several groups have investigated the structure-activity relationships of this polyketide, mostly focusing on the tetrahydropyran core and the distal, oxygenated section of the side chain. Herein, we present the design, synthesis, and conformational studies of a series of analogues to explore substitution on the diene section of GEX1A. We employed computational and high-field NMR studies to describe the analogues' conformational landscape and their relative biological activities to describe their conformational-activity profile. We found that modifications on the diene section brought significant changes to both the molecule's conformation and biological activity.

Indexed as

Fatty AlcoholsPyransDose-Response Relationship, DrugHumansMolecular ConformationMolecular StructureRNA Splicing FactorsStructure-Activity RelationshipFatty AlcoholsherboxidienePyransRNA Splicing FactorscancerconformationGEX1Apolyketidesplicing

Identifiers

PMID42174379

DOI10.1002/cmdc.70309

PMCPMC13206506

What OpenQuestion holds

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LicenceCC BY

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.