Evidence map›Paper›PMID 31140738›Full record

ArticleChemMedChem2019

Combined Scaffold Evaluation and Systems-Level Transcriptome-Based Analysis for Accelerated Lead Optimization Reveals Ribosomal Targeting Spirooxindole Cyclopropanes.

Kevin X Rodriguez, Erin N Howe, Emily P Bacher, Miranda Burnette, Jennifer L Meloche, Jayda Meisel, Patricia Schnepp, Xuejuan Tan, Mayland Chang, Jeremiah Zartman and 2 more

Abstract read
In one paragraph

Article in ChemMedChem, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. GαCell communication and signaling : CCS · 2025
    Article
  3. Article
  4. Article
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

12 authors.

Kevin X RodriguezDepartment of Chemistry and Biochemistry, University of Notre Dame, 305 McCourtney Hall, Notre Dame, IN, 46556, USA.
Erin N HoweDepartment of Biological Sciences, University of Notre Dame, 100 Galvin Life Science Center, Notre Dame, IN, 46556, USA.
Emily P BacherDepartment of Chemistry and Biochemistry, University of Notre Dame, 305 McCourtney Hall, Notre Dame, IN, 46556, USA.
Miranda BurnetteDepartment of Chemical and Biological Engineering, University of Notre Dame, 182 Fitzpatrick Hall, Notre Dame, IN, 46556, USA.
Jennifer L MelocheDepartment of Chemistry and Biochemistry, University of Notre Dame, 305 McCourtney Hall, Notre Dame, IN, 46556, USA.
Jayda MeiselDepartment of Chemistry and Biochemistry, University of Notre Dame, 305 McCourtney Hall, Notre Dame, IN, 46556, USA.
Patricia SchneppDepartment of Biological Sciences, University of Notre Dame, 100 Galvin Life Science Center, Notre Dame, IN, 46556, USA.
Xuejuan TanDepartment of Biological Sciences, University of Notre Dame, 100 Galvin Life Science Center, Notre Dame, IN, 46556, USA.
Mayland ChangDepartment of Chemistry and Biochemistry, University of Notre Dame, 305 McCourtney Hall, Notre Dame, IN, 46556, USA.
Jeremiah ZartmanDepartment of Chemical and Biological Engineering, University of Notre Dame, 182 Fitzpatrick Hall, Notre Dame, IN, 46556, USA.
Siyuan ZhangDepartment of Biological Sciences, University of Notre Dame, 100 Galvin Life Science Center, Notre Dame, IN, 46556, USA.
Brandon L AshfeldDepartment of Chemistry and Biochemistry, University of Notre Dame, 305 McCourtney Hall, Notre Dame, IN, 46556, USA.ORCID 0000-0002-4552-2705

Funding

Viral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Reuben Shaw · 1985 to 2026
$82.8M
Indiana Clinical and Translational Sciences InstituteTL1TR001107 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI DENNE, SCOTT C., SHEKHAR, ANANTHA · 2013 to 2017
$2.0M
Novel roles of endosome-mediated receptor recycling during brain metastatic outgrowthF32CA210583 · NCI · UNIVERSITY OF NOTRE DAME · PI HOWE, ERIN NICOLE · 2016 to 2019
$165k
American Cancer Society Institutional Research Grant IRG-14-195-01Indiana Clinical and Translational Sciences Institute TL1R001107National Science Foundation CHE-1056242 and CHE-1665440NCI NIH HHS F32 CA210583NIH HHS 1F32CA210583NIH HHS Chemistry, Biochemistry, Biology Training GrantWalther Cancer Foundation Advancing Basic Cancer Research ProgramWalther Cancer Foundation ENSCCII Training Grant
6 · The paper itself

Abstract

With evolutionary drug resistance impacting efforts to treat disease, the need for small molecules that exhibit novel molecular mechanisms of action is paramount. In this study, we combined scaffold-directed synthesis with a hybrid experimental and transcriptome analysis to identify bis-spirooxindole cyclopropanes that inhibit cancer cell proliferation through disruption of ribosomal function. These findings demonstrate the value of an integrated, biologically inspired synthesis and assay strategy for the accelerated identification of first-in-class cancer therapeutic candidates.

Indexed as

Antineoplastic AgentsCell ProliferationCyclopropanesDose-Response Relationship, DrugDrug Screening Assays, AntitumorHumansMolecular StructureOxindolesRibosomesRNA, NeoplasmSpiro CompoundsStructure-Activity RelationshipTranscriptomeTumor Cells, CulturedAntineoplastic AgentsCyclopropanesOxindolesRNA, NeoplasmSpiro Compoundsdrug discoverymechanism of actionnatural productsspirooxindolestranscriptome network

Identifiers

PMID31140738
PMCPMC6750968

What OpenQuestion holds

Textmetadata
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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.