Evidence map›Paper›PMID 35491396›Full record

ArticleChemMedChem2022

Anticancer Agents Derived from Cyclic Thiosulfonates: Structure-Reactivity and Structure-Activity Relationships.

Amanda F Ghilardi, Elham Yaaghubi, Renan B Ferreira, Mary E Law, Yinuo Yang, Bradley J Davis, Christopher M Schilson, Ion Ghiviriga, Adrian E Roitberg, Brian K Law and 1 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ChemMedChem, 2022. 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
1.4field-weighted citation impact, top 19% of its field
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, 9 citations in OpenAlex.

  1. Article
  2. Review
  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

11 authors at 1 institution in 1 country.

Amanda F GhilardiDepartment of Chemistry, University of Florida, Gainesville, FL, 32611, USA.ORCID 0000-0002-8080-3713
Elham YaaghubiDepartment of Chemistry, University of Florida, Gainesville, FL, 32611, USA.ORCID 0000-0003-1821-1052
Renan B FerreiraDepartment of Chemistry, University of Florida, Gainesville, FL, 32611, USA.ORCID 0000-0001-5205-659X
Mary E LawDepartment of Pharmacology and Therapeutics, University of Florida, Gainesville, FL, 32610, USA.ORCID 0000-0002-6625-0534
Yinuo YangDepartment of Chemistry, University of Florida, Gainesville, FL, 32611, USA.
Bradley J DavisDepartment of Pharmacology and Therapeutics, University of Florida, Gainesville, FL, 32610, USA.
Christopher M SchilsonDepartment of Chemistry, University of Florida, Gainesville, FL, 32611, USA.
Ion GhivirigaDepartment of Chemistry, University of Florida, Gainesville, FL, 32611, USA.ORCID 0000-0001-5812-5170
Adrian E RoitbergDepartment of Chemistry, University of Florida, Gainesville, FL, 32611, USA.ORCID 0000-0003-3963-8784
Brian K LawDepartment of Pharmacology and Therapeutics, University of Florida, Gainesville, FL, 32610, USA.ORCID 0000-0002-8411-6531
Ronald K CastellanoDepartment of Chemistry, University of Florida, Gainesville, FL, 32611, USA.ORCID 0000-0003-4322-9932
University of Florida · US

Funding

Acquisition of a Q Exactive HF Hybrid Quadrupole-OrbitrapS10OD021758 · OD · UNIVERSITY OF FLORIDA · PI BASSO, KARI B · 2017 to 2017
$600k
Regulation of Death Receptor 5 folding and apoptotic signaling by AGR2R21CA252400 · NCI · UNIVERSITY OF FLORIDA · PI LAW, BRIAN K. · 2020 to 2020
$389k
NCI NIH HHS R21 CA252400NIH HHS S10 OD021758
6 · The paper itself

Abstract

Reported are structure-property-function relationships associated with a class of cyclic thiosulfonate molecules-disulfide-bond disrupting agents (DDAs)-with the ability to downregulate the Epidermal Growth Factor Receptor (HER) family in parallel and selectively induce apoptosis of EGFR+ or HER2+ breast cancer cells. Recent findings have revealed that the DDA mechanism of action involves covalent binding to the thiol(ate) from the active site cysteine residue of members of the protein disulfide isomerase (PDI) family. Reported is how structural modifications to the pharmacophore can alter the anticancer activity of cyclic thiosulfonates by tuning the dynamics of thiol-thiosulfonate exchange reactions, and the studies reveal a correlation between the biological potency and thiol-reactivity. Specificity of the cyclic thiosulfonate ring-opening reaction by a nucleophilic attack can be modulated by substituent addition to a parent scaffold. Lead compound optimization efforts are also reported, and have resulted in a considerable decrease of the IC

Indexed as

Antineoplastic AgentsCysteineProtein Disulfide-IsomerasesStructure-Activity RelationshipSulfhydryl CompoundsAntineoplastic AgentsCysteineProtein Disulfide-IsomerasesSulfhydryl CompoundsAnticancerBreast cancerCyclic thiosulfonateProtein disulfide isomerase inhibitorsThiol reactivityThiosulfonateTunable ring opening

Identifiers

PMID35491396
PMCPMC9308679
OpenAlexW4225270164

What OpenQuestion holds

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Read underepoch 390

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.