Evidence map›Paper›PMID 37552215›Full record

ArticleChemMedChem2023

Linear (-)-Zampanolide: Flexibility in Conformation-Activity Relationships.

Christian A Umaña, Jeffrey L Henry, Claire T Saltzman, Dan L Sackett, Lisa M Jenkins, Richard E Taylor

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ChemMedChem, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

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, IN 46556-5670, USA.
Jeffrey L HenryDepartment of Chemistry and Biochemistry and the Warren Center for Drug Discovery, University of Notre Dame, Notre Dame, IN 46556-5670, USA.
Claire T SaltzmanDepartment of Chemistry and Biochemistry and the Warren Center for Drug Discovery, University of Notre Dame, Notre Dame, IN 46556-5670, USA.
Dan L SackettEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Lisa M JenkinsCenter for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Richard E TaylorDepartment of Chemistry and Biochemistry and the Warren Center for Drug Discovery, University of Notre Dame, Notre Dame, IN 46556-5670, USA.ORCID 0000-0003-1146-7493

Funding

Microtubule regulation by small molecules.ZIAHD008765 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI SACKETT, DAN L · 2009 to 2025
$8.9M
Chemistry-Biochemistry-Biology Training Program at Notre DameT32GM075762 · NIGMS · UNIVERSITY OF NOTRE DAME · PI CHANG, MAYLAND F, MOBASHERY, SHAHRIAR · 2007 to 2021
$3.7M
Synthesis and Biosynthesis of Pyran and Spiroketal Structural UnitsR01GM084922 · NIGMS · UNIVERSITY OF NOTRE DAME · PI TAYLOR, RICHARD E. · 2010 to 2013
$1.1M
NIGMS NIH HHS R01 GM084922NIGMS NIH HHS T32 GM075762NIH HHS GM084922
6 · The paper itself

Abstract

Through an understanding of the conformational preferences of the polyketide natural product (-)-zampanolide, and the structural motifs that control these preferences, we developed a linear zampanolide analogue that exhibits potent cytotoxicity against cancer cell lines. This discovery provides a set of three structural handles for further structure-activity relationship (SAR) studies of this potent microtubule-stabilizing agent. Moreover, it provides additional evidence of the complex relationship between ligand preorganization, conformational flexibility, and biological potency. In contrast to medicinal chemistry dogma, these results demonstrate that increased overall conformational flexibility is not necessarily detrimental to protein binding affinity and biological activity.

Indexed as

MacrolidesPolyketidesMolecular ConformationStructure-Activity RelationshipMacrolidesPolyketideszampanolideconformationlinear analoguesmacrocyclespolyketideszampanolide

Identifiers

PMID37552215
PMCPMC10615712

What OpenQuestion holds

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Registered trials

None linked

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.