Evidence map›Paper›PMID 30413713›Full record

ArticleNature communications2018

Design and 22-step synthesis of highly potent D-ring modified and linker-equipped analogs of spongistatin 1.

Linda M Suen, Makeda A Tekle-Smith, Kevin S Williamson, Joshua R Infantine, Samuel K Reznik, Paul S Tanis, Tyler D Casselman, Dan L Sackett, James L Leighton

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

9 authors.

Linda M SuenDepartment of Chemistry, Columbia University, New York, NY, 10027, USA.
Makeda A Tekle-SmithDepartment of Chemistry, Columbia University, New York, NY, 10027, USA.
Kevin S WilliamsonDepartment of Chemistry, Columbia University, New York, NY, 10027, USA.
Joshua R InfantineDepartment of Chemistry, Columbia University, New York, NY, 10027, USA.
Samuel K ReznikDepartment of Chemistry, Columbia University, New York, NY, 10027, USA.
Paul S TanisDepartment of Chemistry, Columbia University, New York, NY, 10027, USA.
Tyler D CasselmanDepartment of Chemistry, Columbia University, New York, NY, 10027, USA.
Dan L SackettEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, USA. sackettd@mail.nih.gov.
James L LeightonDepartment of Chemistry, Columbia University, New York, NY, 10027, USA. jll43@columbia.edu.ORCID http://orcid.org/0000-0002-9061-8327

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
Asymmetric Synthesis of Marcolide AntibioticsR01GM058133 · NIGMS · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI LEIGHTON, JAMES L · 1998 to 2017
$4.7M
Efficient Synthesis of the Spongistatin EF Ring Segment and Analogue SAR StudyF32GM090487 · NIGMS · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI TANIS, PAUL STEVEN · 2010 to 2012
$132k
NIGMS NIH HHS F32 GM090487NIGMS NIH HHS R01 GM058133
6 · The paper itself

Abstract

Spongistatin 1 is among the most potent anti-proliferative agents ever discovered rendering it an attractive candidate for development as a payload for antibody-drug conjugates and other targeted delivery approaches. Unfortunately, it is unavailable from natural sources and its size and complex stereostructure render chemical synthesis highly time- and resource-intensive. As a result, the design and synthesis of more acid-stable and linker functional group-equipped analogs that retain the low picomolar potency of the parent natural product requires more efficient and step-economical synthetic access. Using uniquely enabling direct complex fragment coupling crotyl- and alkallylsilylation reactions, we report a 22-step synthesis of a rationally designed D-ring modified analog of spongistatin 1 that is characterized by GI

Indexed as

Drug DesignAntimitotic AgentsCell Line, TumorCell ProliferationHumansMacrolidesPolyether ToxinsAntimitotic AgentsMacrolidesPolyether Toxinsspongistatin 1

Identifiers

PMID30413713
PMCPMC6226463

What OpenQuestion holds

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Registered trials

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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.