Evidence map›Paper›PMID 40776603›Full record

ArticleChemMedChem2025

Structure-Based Drug Design of Novel Heterocyclic Scaffolds as TgCDPK1 Inhibitors.

Anoopjit Singh Kooner, Mariah Norman, Igi Vilza, Michael P Mannino, Mary Savari Dhason, Jon Helander, Shrushti Patil, L David Sibley, James W Janetka

Abstract read
In one paragraph

Article in ChemMedChem, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

9 authors.

Anoopjit Singh KoonerDepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, 63110, USA.ORCID https://orcid.org/0000-0003-1747-5689
Mariah NormanDepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Igi VilzaDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.ORCID https://orcid.org/0000-0001-9939-625X
Michael P ManninoDepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, 63110, USA.ORCID https://orcid.org/0000-0002-8135-1675
Mary Savari DhasonDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Jon HelanderDepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Shrushti PatilDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.ORCID https://orcid.org/0009-0004-1527-0705
L David SibleyDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
James W JanetkaDepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, 63110, USA.ORCID https://orcid.org/0000-0002-9888-5411

Funding

Optimizing CDPK1 inhibitors for chronic toxoplasmosisR01AI164473 · NIAID · WASHINGTON UNIVERSITY · PI James W Janetka, L. David Sibley · 2022 to 2026
$3.9M
NIAID NIH HHS R01 AI164473NIH HHS 1R01AI164473
6 · The paper itself

Abstract

Toxoplasmosis is caused by the protozoan parasite Toxoplasma gondii and poses grave health concern for immunocompromised patients. T. gondii has a family of calcium dependent protein kinases (CDPKs) that control a variety of critical processes. Among these, TgCDPK1 is required for parasite motility, cell invasion, and egress and hence is essential both for in vitro growth of T. gondii and to cause infections in animals. Using existing X-ray cocrystal structures of pyrazolopyrimidine (PP) inhibitors bound to TgCDPK1, six new chemical series of inhibitors are rationally designed. The synthesis of analogs based on the most promising novel series is pursued, which resulted in potent TgCDPK1 inhibitors that effectively block parasite growth in cells. The resulting lead compounds 44 and 45 belonging to the imidazopyrazine chemical series demonstrate the promising potential of this new class of inhibitors for the treatment and possible cure of the Toxoplasmosis.

Indexed as

Drug DesignHeterocyclic CompoundsProtein Kinase InhibitorsProtein KinasesProtozoan ProteinsToxoplasmaAnimalsCalcium-Calmodulin-Dependent Protein KinasesCrystallography, X-RayHumansModels, MolecularMolecular StructurePyrazolesPyrimidinesStructure-Activity RelationshipCalcium-Calmodulin-Dependent Protein KinasesHeterocyclic CompoundsProtein Kinase InhibitorsProtein KinasesProtozoan ProteinsPyrazolesPyrimidinescalcium dependent protein kinase 1kinase inhibitorstructure‐based drug designtoxoplasmosis

Identifiers

PMID40776603
PMCPMC12402975

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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.