Evidence map›Paper›PMID 26552986›Full record

ArticleAntimicrobial agents and chemotherapy2016

Inhibition of Calcium-Dependent Protein Kinase 1 (CDPK1) In Vitro by Pyrazolopyrimidine Derivatives Does Not Correlate with Sensitivity of Cryptosporidium parvum Growth in Cell Culture.

Theresa B Kuhlenschmidt, Florentine U Rutaganira, Shaojun Long, Keliang Tang, Kevan M Shokat, Mark S Kuhlenschmidt, L David Sibley

Open access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
1.9field-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

33 citing papers in PubMed, 41 citations in OpenAlex.

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  19. Anti-protozoal activity of Thymol and a Thymol ester against Cryptosporidium parvum in cell culture.International journal for parasitology. Drugs and drug resistance · 2021
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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

7 authors at 4 institutions in 1 country.

Theresa B KuhlenschmidtDepartment of Pathobiology, University of Illinois College of Veterinary Medicine, Urbana, Illinois, USA.
Florentine U RutaganiraHoward Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California, USA.
Shaojun LongDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA.
Keliang TangDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA.
Kevan M ShokatHoward Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California, USA.
Mark S KuhlenschmidtDepartment of Pathobiology, University of Illinois College of Veterinary Medicine, Urbana, Illinois, USA.
L David SibleyDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA sibley@wustl.edu.
Washington University in St. Louis · USIllinois College · USHoward Hughes Medical Institute · USUniversity of California, San Francisco · US

Funding

PROTEIN SECRETION &INTRACELLULAR SURVIVAL BY TOXOPLASMAR01AI034036 · NIAID · WASHINGTON UNIVERSITY · PI SIBLEY, L. DAVID · 1993 to 2019
$7.9M
RESEARCH TRAINING IN CHEMISTRY AND CHEMICAL BIOLOGYT32GM064337 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CRAIK, CHARLES SCOTT · 2002 to 2021
$7.8M
DESIGNING SELECTIVE INHIBITORS OF CALCIUM-DEPENDENT KINASES IN PARASITESR01AI094098 · NIAID · WASHINGTON UNIVERSITY · PI SIBLEY, L. DAVID · 2012 to 2015
$1.6M
NIAID NIH HHS AI094098NIAID NIH HHS R01 AI034036NIAID NIH HHS R01 AI094098NIGMS NIH HHS T32 GM064337
6 · The paper itself

Abstract

Cryptosporidiosis is a serious diarrheal disease in immunocompromised patients and malnourished children, and treatment is complicated by a lack of adequate drugs. Recent studies suggest that the natural occurrence of a small gatekeeper residue in serine threonine calcium-dependent protein kinase 1 (CDPK1) of Cryptosporidium parvum might be exploited to target this enzyme and block parasite growth. Here were explored the potency with which a series of pyrazolopyrimidine analogs, which are selective for small gatekeeper kinases, inhibit C. parvum CDPK1 and block C. parvum growth in tissue culture in vitro. Although these compounds potently inhibited kinase activity in vitro, most had no effect on parasite growth. Moreover, among those that were active against parasite growth, there was a very poor correlation with their 50% inhibitory concentrations against the enzyme. Active compounds also had no effect on cell invasion, unlike the situation in Toxoplasma gondii, where these compounds block CDPK1, prevent microneme secretion, and disrupt cell invasion. These findings suggest that CPDK1 is not essential for C. parvum host cell invasion or growth and therefore that it is not the optimal target for therapeutic intervention. Nonetheless, several inhibitors with low micromolar 50% effective concentrations were identified, and these may affect other essential targets in C. parvum that are worthy of further exploration.

Indexed as

AnimalsAntiprotozoal AgentsCalcium-Calmodulin-Dependent Protein KinasesCattleCell LineCryptosporidium parvumEpithelial CellsFecesGene ExpressionHumansInhibitory Concentration 50MaleParasitic Sensitivity TestsProtein KinasesProtozoan ProteinsPyrazolesAntiprotozoal AgentsCalcium-Calmodulin-Dependent Protein KinasesProtein KinasesProtozoan ProteinsPyrazolesPyrimidines

Identifiers

PMID26552986
PMCPMC4704151
OpenAlexW2146291612

What OpenQuestion holds

Textmetadata
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.