Evidence map›Paper›PMID 26962873›Full record

ArticleJournal of biomolecular screening2016

A High-Throughput Screening Strategy to Identify Protein-Protein Interaction Inhibitors That Block the Fanconi Anemia DNA Repair Pathway.

Andrew F Voter, Kelly A Manthei, James L Keck

Open access · hybridAbstract read
In one paragraph

Article in Journal of biomolecular screening, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

25 citing papers in PubMed, 42 citations in OpenAlex.

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  19. Practical Model Selection for Prospective Virtual Screening.Journal of chemical information and modeling · 2019
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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

3 authors at 2 institutions in 1 country.

Andrew F VoterDepartment of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Kelly A MantheiLife Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
James L KeckDepartment of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA jlkeck@wisc.edu.
University of Wisconsin–Madison · USUniversity of Michigan–Ann Arbor · US

Funding

Institutional Clinical and Translational Science AwardUL1TR000427 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI DREZNER, MARC KENNETH · 2012 to 2016
$32.2M
GRADUATE TRAINING IN MOLECULAR BIOSCIENCEST32GM007215 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI HULL, CHRISTINA M · 1985 to 2018
$22.5M
INTEGRATED TRAINING FOR PHYSICIAN-SCIENTISTST32GM008692 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI BURKARD, MARK E · 1998 to 2020
$10.3M
Structure and Function of the Bacterial PrimosomeR01GM098885 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI James L Keck · 2012 to 2026
$4.0M
Targeting the Fanconi Anemia/Bloom Dissolvasome protein interface as a discoveryR21CA178475 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI KECK, JAMES L · 2013 to 2014
$352k
Identification of chemosensitizing agents that block DNA repair by the Fanconi Anemia/Bloom Dissolvasome complexF30CA210465 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI VOTER, ANDREW FORD · 2016 to 2019
$118k
ACQUISITION OF MASS SPECTROMETER FOR CORE FACILITYS10RR013790 · NCRR · UNIVERSITY OF WISCONSIN MADISON · PI RAINES, RONALD T · 1999 to 1999
–
NCATS NIH HHS UL1 TR000427NCI NIH HHS F30 CA210465NCI NIH HHS R21 CA178475NCRR NIH HHS S10 RR013790NIGMS NIH HHS R01 GM098885NIGMS NIH HHS T32 GM007215NIGMS NIH HHS T32 GM008692
6 · The paper itself

Abstract

Induction of the Fanconi anemia (FA) DNA repair pathway is a common mechanism by which tumors evolve resistance to DNA crosslinking chemotherapies. Proper execution of the FA pathway requires interaction between the FA complementation group M protein (FANCM) and the RecQ-mediated genome instability protein (RMI) complex, and mutations that disrupt FANCM/RMI interactions sensitize cells to DNA crosslinking agents. Inhibitors that block FANCM/RMI complex formation could be useful therapeutics for resensitizing tumors that have acquired chemotherapeutic resistance. To identify such inhibitors, we have developed and validated high-throughput fluorescence polarization and proximity assays that are sensitive to inhibitors that disrupt interactions between the RMI complex and its binding site on FANCM (a peptide referred to as MM2). A pilot screen of 74,807 small molecules was performed using the fluorescence polarization assay. Hits from the primary screen were further tested using the proximity assay, and an orthogonal proximity assay was used to assess inhibitor selectivity. Direct physical interaction between the RMI complex and the most selective inhibitor identified through the screening process was measured by surface plasmon resonance and isothermal titration calorimetry. Observation of direct binding by this small molecule validates the screening protocol.

Indexed as

Antineoplastic AgentsDNA DamageDNA HelicasesDNA RepairDrug Screening Assays, AntitumorFanconi AnemiaHigh-Throughput Screening AssaysHumansMultiprotein ComplexesProtein Interaction MapsRecQ HelicasesAntineoplastic AgentsDNA HelicasesFANCM protein, humanMultiprotein ComplexesRecQ HelicasesDNA repairFanconi anemiaprotein interaction inhibitor screen

Identifiers

PMID26962873
PMCPMC5038921
OpenAlexW2296521590

What OpenQuestion holds

Textmetadata
LicenceTDM
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.