Evidence map›Paper›PMID 31712618›Full record

ArticleScientific reports2019

Binding and structural analyses of potent inhibitors of the human Ca

Gerson S Profeta, Caio V Dos Reis, André da S Santiago, Paulo H C Godoi, Angela M Fala, Carrow I Wells, Roger Sartori, Anita P T Salmazo, Priscila Z Ramos, Katlin B Massirer and 4 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

10 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
  2. Review
  3. The role of CaMKK2 in Golgi-associated vesicle trafficking.Biochemical Society transactions · 2023
    Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
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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

14 authors at 3 institutions in 3 countries.

Gerson S ProfetaCentro de Química Medicinal (CQMED), Centro de Biologia Molecular e Engenharia Genética (CBMEG), Universidade Estadual de Campinas (UNICAMP), Campinas, SP, 13083-875, Brazil.
Caio V Dos ReisCentro de Química Medicinal (CQMED), Centro de Biologia Molecular e Engenharia Genética (CBMEG), Universidade Estadual de Campinas (UNICAMP), Campinas, SP, 13083-875, Brazil.
André da S SantiagoCentro de Química Medicinal (CQMED), Centro de Biologia Molecular e Engenharia Genética (CBMEG), Universidade Estadual de Campinas (UNICAMP), Campinas, SP, 13083-875, Brazil.ORCID http://orcid.org/0000-0002-3973-3370
Paulo H C GodoiCentro de Química Medicinal (CQMED), Centro de Biologia Molecular e Engenharia Genética (CBMEG), Universidade Estadual de Campinas (UNICAMP), Campinas, SP, 13083-875, Brazil.
Angela M FalaCentro de Química Medicinal (CQMED), Centro de Biologia Molecular e Engenharia Genética (CBMEG), Universidade Estadual de Campinas (UNICAMP), Campinas, SP, 13083-875, Brazil.
Carrow I WellsStructural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.ORCID http://orcid.org/0000-0003-4799-6792
Roger SartoriStructural Genomics Consortium, Departamento de Genética e Evolução, Instituto de Biologia, UNICAMP, Campinas, SP, 13083-886, Brazil.
Anita P T SalmazoStructural Genomics Consortium, Departamento de Genética e Evolução, Instituto de Biologia, UNICAMP, Campinas, SP, 13083-886, Brazil.
Priscila Z RamosCentro de Química Medicinal (CQMED), Centro de Biologia Molecular e Engenharia Genética (CBMEG), Universidade Estadual de Campinas (UNICAMP), Campinas, SP, 13083-875, Brazil.ORCID http://orcid.org/0000-0001-6716-2504
Katlin B MassirerCentro de Química Medicinal (CQMED), Centro de Biologia Molecular e Engenharia Genética (CBMEG), Universidade Estadual de Campinas (UNICAMP), Campinas, SP, 13083-875, Brazil.
Jonathan M ElkinsStructural Genomics Consortium, Departamento de Genética e Evolução, Instituto de Biologia, UNICAMP, Campinas, SP, 13083-886, Brazil.ORCID http://orcid.org/0000-0003-2858-8929
David H DrewryStructural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.ORCID http://orcid.org/0000-0001-5973-5798
Opher GileadiStructural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.ORCID http://orcid.org/0000-0001-6886-898X
Rafael M CouñagoCentro de Química Medicinal (CQMED), Centro de Biologia Molecular e Engenharia Genética (CBMEG), Universidade Estadual de Campinas (UNICAMP), Campinas, SP, 13083-875, Brazil. rafael.counago@unicamp.br.
Universidade Estadual de Campinas (UNICAMP) · BRUniversity of North Carolina at Chapel Hill · USUniversity of Oxford · GB

Funding

Overall EvaluationP41GM103403 · NIGMS · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2012 to 2017
$14.3M
Creation of in vivo active chemical probes for CAMKK2 to treat cancerR01CA218442 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DREWRY, DAVID HAROLD · 2017 to 2019
$2.0M
Pixel Array Detector for X-ray CrystallographyS10RR029205 · NCRR · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2010 to 2010
$1.8M
NCI NIH HHS R01 CA218442NCRR NIH HHS S10 RR029205NIGMS NIH HHS P41 GM103403Wellcome TrustWellcome Trust 106169/ZZ14/Z
6 · The paper itself

Abstract

Calcium/Calmodulin-dependent Protein Kinase Kinase 2 (CAMKK2) acts as a signaling hub, receiving signals from various regulatory pathways and decoding them via phosphorylation of downstream protein kinases - such as AMPK (AMP-activated protein kinase) and CAMK types I and IV. CAMKK2 relevance is highlighted by its constitutive activity being implicated in several human pathologies. However, at present, there are no selective small-molecule inhibitors available for this protein kinase. Moreover, CAMKK2 and its closest human homolog, CAMKK1, are thought to have overlapping biological roles. Here we present six new co-structures of potent ligands bound to CAMKK2 identified from a library of commercially-available kinase inhibitors. Enzyme assays confirmed that most of these compounds are equipotent inhibitors of both human CAMKKs and isothermal titration calorimetry (ITC) revealed that binding to some of these molecules to CAMKK2 is enthalpy driven. We expect our results to advance current efforts to discover small molecule kinase inhibitors selective to each human CAMKK.

Indexed as

AnimalsCalcium-Calmodulin-Dependent Protein Kinase KinaseDrug DiscoveryHumansLigandsMolecular ConformationMolecular Docking SimulationMolecular Dynamics SimulationProtein BindingProtein Kinase InhibitorsRecombinant ProteinsStructure-Activity RelationshipCalcium-Calmodulin-Dependent Protein Kinase KinaseCAMKK2 protein, humanLigandsProtein Kinase InhibitorsRecombinant Proteins

Identifiers

PMID31712618
PMCPMC6848146
OpenAlexW2988485998

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.