Affinage · Toxoplasma gondii

CDPK1

calcium-dependent protein kinase CDPK1 · UniProt A0A125YH30

Annotated
2026-09-08
75 papers in source corpus 19 papers cited in narrative 19 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TgCDPK1 is an essential calcium-dependent serine/threonine protein kinase in Toxoplasma gondii that transduces intracellular Ca2+ signals into microneme exocytosis, gliding motility, host-cell invasion, and egress (PMID:20485436, PMID:26755159). Its activity is calcium-dependent and independent of calmodulin or phospholipids (PMID:11154702), and calcium is delivered to the kinase upstream via a phospholipase C-generated signal that couples egress triggers to Ca2+-activated CDPK1 (PMID:11526113). Activation is structurally governed by the C-terminal CDPK activation (CAD) domain: in the apo state an N-terminal CAD helix autoinhibits the kinase domain, and Ca2+ binding drives a large CAD reorganization that repositions it away from the substrate site (PMID:20436473); this CAD serves a dual role, both inhibiting and allosterically stabilizing the active kinase, so that derepression alone is insufficient for activation (PMID:26305940). Direct binding of TgDJ-1 through an arginine-dyad phospho-gatekeeper motif further potentiates kinase activity in a calcium- and oxidation-sensitive manner and is required for normal microneme secretion (PMID:28246362). Phosphoproteomic and bio-orthogonal substrate labeling identified 163 CDPK1-dependent substrates, including a HOOK activating adaptor that, together with an FHF-like complex, drives rapid apical microneme trafficking as parasites initiate motility (PMID:23530747, PMID:37933960). Functionally, CDPK1 controls F-actin flux underlying motility (PMID:30753127), acts with partial redundancy in a signaling module with CDPK2A upstream of motility and egress (PMID:37610220), operates in a pathway distinct from CDPK3 (PMID:23149386), and negatively regulates dense granule secretion reciprocally with microneme discharge (PMID:30673152). A unique glycine gatekeeper residue in the ATP-binding site makes TgCDPK1 exquisitely sensitive to bumped kinase inhibitors and analog-sensitive/chemical-genetic approaches (PMID:20436472, PMID:20173034), with TgMAPKL1 identified as a secondary BKI co-target (PMID:40407244).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2001 Medium

    Established that a calcium-dependent kinase activity in Toxoplasma corresponds to TgCDPK1 and phosphorylates specific parasite substrates, linking it to motility and attachment.

    Evidence Biochemical fractionation, in vitro kinase assays, and KT5926 inhibition correlating in vitro and in vivo phosphoproteins in tachyzoites

    PMID:11154702

    Open questions at the time
    • Substrate identities not molecularly defined
    • No genetic evidence for essentiality or in vivo function
  2. 2001 Medium

    Placed CDPK1 downstream of a Ca2+ signal in the egress pathway, defining how an environmental trigger (low host [K+]) is transduced into parasite exit.

    Evidence Pharmacological manipulation of Ca2+, K+, and kinase inhibitors with egress assays

    PMID:11526113

    Open questions at the time
    • The identity of the second parallel egress pathway not resolved
    • Inhibitor selectivity for CDPK1 not genetically confirmed at this stage
  3. 2006 Medium

    Tested whether selective CDPK1 inhibition alone accounts for an imidazopyridine compound's antiparasitic potency, showing it does not and pointing to additional targets.

    Evidence Radiolabeled ligand binding, gatekeeper-pocket mutagenesis, and transgenic G128Q mutant growth assays

    PMID:16765465

    Open questions at the time
    • Additional relevant targets of the compound not identified
    • Overexpression rather than allelic replacement limits interpretation
  4. 2010 High

    Demonstrated genetically and chemical-genetically that CDPK1 is essential for calcium-dependent microneme secretion and hence motility, invasion, and egress.

    Evidence Conditional knockdown plus pyrazolopyrimidine inhibition with resistant gatekeeper-mutant rescue and secretion/motility/invasion/egress assays

    PMID:20485436

    Open questions at the time
    • Direct substrates driving secretion not yet identified
    • Molecular link between kinase activity and vesicle discharge unknown
  5. 2010 High

    Resolved the structural basis of Ca2+-signal transduction by CDPK1, showing CAD-mediated autoinhibition relieved by calcium-driven domain reorganization.

    Evidence X-ray crystallography of apo and Ca2+-bound TgCDPK1

    PMID:20436473

    Open questions at the time
    • Whether derepression alone suffices for activation not addressed
    • Dynamics in solution not captured by static structures
  6. 2010 High

    Defined the unique glycine gatekeeper as the structural determinant of BKI selectivity and validated CDPK1 as the in vivo BKI target.

    Evidence Co-crystal structures with BKIs, in vitro inhibition, and glycine-to-methionine gatekeeper mutant parasites

    PMID:20436472

    Open questions at the time
    • Whether other kinases share BKI sensitivity not excluded
    • Relationship to microneme vs motility phenotypes not dissected here
  7. 2010 Medium

    Provided evidence that CDPK1 acts in gliding motility independently of, or downstream of, microneme secretion.

    Evidence Analog-sensitive 1NM-PP1 inhibition with G128M mutant, motility and micronemal secretion assays

    PMID:20173034

    Open questions at the time
    • Partial contradiction with other work reporting a secretion block
    • Molecular effectors of the motility role not defined
  8. 2012 High

    Distinguished CDPK1 from CDPK3 as controllers of separate calcium pathways, with CDPK1 universally required for microneme secretion and invasion.

    Evidence Chemical-genetic inhibition of analog-sensitive CDPK1 and CDPK3 alleles with secretion, invasion, and egress assays and PKG activation

    PMID:23149386

    Open questions at the time
    • Molecular basis for pathway divergence not defined
    • How PKG compensates for CDPK3 not mechanistically resolved
  9. 2013 High

    Defined the CDPK1 substrate repertoire by identifying 163 substrates via bio-orthogonal thiophosphorylation, mapping the kinase's downstream reach.

    Evidence Analog-sensitive kinase with ATPgammaS analogue, phosphoproteomics, and in vitro/in vivo validation

    PMID:23530747

    Open questions at the time
    • Functional roles of most substrates untested
    • Temporal order of phosphorylation events not resolved
  10. 2015 High

    Revised the activation model, showing the CAD domain both inhibits and allosterically activates the kinase, and that derepression alone is insufficient.

    Evidence VHH antibody screening, crystal structure of the TgCDPK1-1B7 complex, molecular dynamics, and domain-deletion kinase assays

    PMID:26305940

    Open questions at the time
    • Physiological modulators of allosteric stabilization not identified here
    • Therapeutic exploitation of the conformational epitope untested in vivo
  11. 2016 Medium

    Confirmed CDPK1 essentiality by complete gene deletion, establishing it as a non-redundant requirement for parasite growth.

    Evidence CRISPR/Cas9 deletion with Cre-loxP marker recycling and plaque assays, obtainable only with complementation

    PMID:26755159

    Open questions at the time
    • Stage-specific requirements not dissected
    • Essential substrate(s) not pinpointed
  12. 2017 High

    Identified TgDJ-1 as a direct binding partner that potentiates CDPK1 activity in a redox- and calcium-sensitive manner required for microneme secretion.

    Evidence Crystal structure of TgDJ-1, co-immunoprecipitation, arginine-dyad mutagenesis, in vitro kinase assays, and TgDJ-1 knockout secretion assays

    PMID:28246362

    Open questions at the time
    • How oxidation modulates the interaction mechanistically not fully resolved
    • Physiological trigger integrating redox and Ca2+ signals unknown
  13. 2017 Medium

    Showed CDPK1 (with CDPK3) participates in dampening the cytosolic Ca2+ signal before egress, expanding its role beyond effector output to signal shaping.

    Evidence GCaMP6 live Ca2+ imaging with pharmacological CDPK1/CDPK3 inhibition

    PMID:27781359

    Open questions at the time
    • Substrates mediating signal quenching not identified
    • Direct vs indirect contribution of CDPK1 not separated from CDPK3
  14. 2019 Medium

    Placed CDPK1 as a regulator of F-actin flux underlying motility, invasion, and egress, acting alongside PKG and AKMT independently of microneme secretion.

    Evidence F-actin chromobody live imaging, formin disruption, and PKG/CDPK1 inhibitor epistasis with AKMT mutants

    PMID:30753127

    Open questions at the time
    • Direct CDPK1 substrates controlling actin flux not identified
    • How phosphorylation and methylation inputs are integrated unclear
  15. 2019 Medium

    Established that CDPK1 negatively regulates dense granule exocytosis in response to Ca2+, providing reciprocal control with microneme discharge.

    Evidence Dense granule secretion assays with Ca2+ manipulation and CDPK1/CDPK3 inhibition

    PMID:30673152

    Open questions at the time
    • Substrates mediating dense granule suppression unknown
    • CDPK1-specific contribution not fully separated from CDPK3
  16. 2020 Medium

    Identified CDPK1 as a cellular target of the compound ENH1 responsible for its egress block, while showing calcium-homeostasis and viability effects are CDPK1-independent.

    Evidence Thermal proteome profiling, in vitro kinase assay, sensitive vs resistant CDPK1 allele comparison, and egress assays

    PMID:32597628

    Open questions at the time
    • Additional ENH1 targets not identified
    • Mechanistic basis of CDPK1-independent effects unknown
  17. 2023 High

    Connected CDPK1 kinase activity to a concrete trafficking machine by identifying a HOOK adaptor substrate and an FHF-like complex driving rapid apical microneme delivery for motility initiation.

    Evidence Sub-minute phosphoproteomics, bio-orthogonal substrate labeling, conditional depletion of HOOK and FTS, and secretion/invasion/live imaging

    PMID:37933960

    Open questions at the time
    • Motor/dynein activation steps downstream of HOOK phosphorylation not fully resolved
    • Roles of the two parasite-specific FHF components undefined
  18. 2023 Medium

    Defined CDPK2A as functioning with partial redundancy upstream of or in parallel with CDPK1 in the motility/egress module.

    Evidence Analog-sensitive alleles, auxin-inducible degron depletion, and epistasis with secretion, motility, and egress assays

    PMID:37610220

    Open questions at the time
    • Shared vs distinct substrates of CDPK1 and CDPK2A not defined
    • Precise epistatic order not fully resolved
  19. 2025 Medium

    Revealed that BKIs dually target CDPK1 and TgMAPKL1, refining the mechanism of BKI action and resistance.

    Evidence Chemical mutagenesis forward screen, whole-genome sequencing, and site-directed CDPK1 (G128M)/TgMAPKL1 (L162Q) resistance mutation validation with inhibition assays

    PMID:40407244

    Open questions at the time
    • Relative contribution of each kinase to killing not quantified
    • Whether TgMAPKL1 acts in the CDPK1 pathway unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The direct substrates linking CDPK1 to F-actin flux, dense granule suppression, and Ca2+ signal quenching, and how CDPK1 integrates with CDPK2A/CDPK3/PKG signaling, remain to be mechanistically defined.
  • Effector substrates for actin regulation and secretion suppression unidentified
  • Integration among the CDPK1/CDPK2A/CDPK3/PKG modules not resolved
  • Physiological inputs controlling the TgDJ-1/redox potentiation unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
AKMT (CO-REGULATOR OF F-ACTIN FLUX)CDPK2A (PARTIALLY REDUNDANT MODULE PARTNER)CDPK3 (PARALLEL CALCIUM PATHWAY)HOOK ACTIVATING ADAPTOR (SUBSTRATE)PKG (FUNCTIONAL EPISTASIS IN MOTILITY/EGRESS)TGDJ-1 (DIRECT BINDER, POTENTIATES KINASE ACTIVITY)TGMAPKL1 (SECONDARY BKI CO-TARGET)
Complex memberships
FHF-like complex (HOOK, FTS homolog, two parasite-specific proteins) acting downstream of CDPK1TgCDPK1-1B7 VHH antibody inhibitory complex (experimental)TgCDPK1-TgDJ-1 complex (direct binding via arginine-dyad phospho-gatekeeper motif)

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 TgCDPK1 protein is expressed in Toxoplasma tachyzoites, exhibits calcium-dependent kinase activity that does not require calmodulin or phospholipids, co-fractionates with KT5926-sensitive kinase activity, and phosphorylates three parasite proteins in vitro that correspond to the three KT5926-sensitive phosphoproteins detected in vivo, implicating it in regulating motility and host cell attachment. Biochemical fractionation, in vitro kinase assay, pharmacological inhibition with KT5926 The Journal of biological chemistry Medium 11154702
2001 Egress-triggering reduction in host cell [K+] activates a phospholipase C in Toxoplasma leading to increased cytoplasmic [Ca2+], which then activates TgCDPK1 as one of at least two downstream signaling pathways required for parasite egress; buffering cytoplasmic Ca2+ blocks egress and calcium ionophores bypass the need for low [K+]. Pharmacological manipulation of Ca2+, potassium concentrations, and kinase inhibitors; egress assay The Journal of biological chemistry Medium 11526113
2010 TgCDPK1 is an essential regulator of calcium-dependent microneme exocytosis; conditional suppression of TgCDPK1 blocks calcium-dependent secretion from micronemes, abolishing parasite motility, host-cell invasion, and egress. A glycine gatekeeper mutant (resistant to pyrazolopyrimidine inhibitors) restored sensitivity reversal, confirming TgCDPK1 as the specific in vivo target. Conditional knockdown (promoter replacement), chemical-genetic inhibition with pyrazolopyrimidine compounds, mutant rescue experiment, microneme secretion assay, motility/invasion/egress assays Nature High 20485436
2010 Crystal structures of TgCDPK1 in autoinhibited (apo) and calcium-activated conformations reveal that the C-terminal CDPK activation domain (CAD) in the apo form contains a long N-terminal helix that inhibits the kinase domain analogously to CaMKII autoinhibition; calcium binding triggers major reorganization of the CAD to a position remote from the substrate-binding site, constituting a distinct mechanism of calcium-signal transduction. X-ray crystallography of apo and calcium-bound forms of TgCDPK1 Nature structural & molecular biology High 20436473
2010 TgCDPK1 contains a unique glycine gatekeeper residue in its ATP-binding site that confers nanomolar sensitivity to bumped kinase inhibitors (BKIs); co-crystal structures of TgCDPK1 with BKIs confirm the structural basis for selectivity, and T. gondii expressing a glycine-to-methionine gatekeeper mutant shows significantly decreased BKI sensitivity in vivo, confirming TgCDPK1 as the BKI target mediating early infection inhibition. Co-crystal structure determination, in vitro kinase inhibition assays, gatekeeper mutant parasite line generation and growth inhibition assays Nature structural & molecular biology High 20436472
2010 Inhibition of TgCDPK1 by 1NM-PP1 blocks gliding motility without inhibiting micronemal secretion, suggesting TgCDPK1 has a role in gliding motility downstream of or independent of microneme secretion; a G128M gatekeeper mutation in TgCDPK1 confers resistance to 1NM-PP1. Chemical-genetic inhibition with analog-sensitive kinase approach, motility assay, micronemal secretion assay, site-directed mutagenesis Eukaryotic cell Medium 20173034
2012 TgCDPK1 and TgCDPK3 control distinct calcium signaling pathways: TgCDPK1 is required universally for microneme secretion and for invasion, whereas TgCDPK3 is required for ionophore-induced egress but not for invasion; cGMP-dependent protein kinase (PKG) activation can partially compensate for TgCDPK3 inhibition during egress. Chemical-genetic inhibition of analog-sensitive CDPK1 and CDPK3 alleles; microneme secretion assay; invasion assay; egress assay; pharmacological activation of PKG The EMBO journal High 23149386
2013 Using an analog-sensitive TgCDPK1 allele and a synthetic ATPγS analogue complementary to the expanded glycine-gatekeeper ATP pocket, 163 CDPK1 substrates were identified by selective thiophosphorylation; predicted phosphorylation sites were concordant with TgCDPK1 in vitro substrate preference, and phosphorylation of identified substrates was confirmed to be CDPK1-dependent both in vitro and in vivo. Chemical-genetic substrate identification (analog-sensitive kinase + thiophosphate labeling), phosphoproteomics, in vitro kinase assays, in vivo validation ACS chemical biology High 23530747
2015 Removal of the autoinhibitory domain from TgCDPK1 alone is insufficient for kinase activation; the regulatory (CAD) domain plays a dual role, both inhibiting and allosterically activating the kinase domain in a Ca2+-dependent manner. A VHH antibody (1B7) that binds TgCDPK1 in a conformation-dependent manner potently inhibits it by disrupting this allosteric stabilization, as revealed by the crystal structure of the complex and molecular dynamics simulations. VHH antibody library screening, crystal structure of TgCDPK1-1B7 complex, molecular dynamics simulation, in vitro kinase activity assays with domain deletion mutants Proceedings of the National Academy of Sciences of the United States of America High 26305940
2016 CDPK1 is essential in T. gondii; CRISPR/Cas9-based complete gene deletion confirmed CDPK1 essentiality for parasite growth in vitro, as deletions could not be obtained without complementation. CRISPR/Cas9 gene deletion with Cre-loxP marker recycling, plaque assay Infection and immunity Medium 26755159
2017 TgDJ-1 directly binds to TgCDPK1 through an arginine dyad phospho-gatekeeper motif; the interaction is sensitive to oxidation and calcium, potentiates CDPK1 kinase activity, and is required for normal microneme exocytosis. Genetic deletion of TgDJ-1 upregulates CDPK1 expression, and disruption of the TgDJ-1/CDPK1 complex prevents microneme secretion in vivo. X-ray crystal structure of TgDJ-1, co-immunoprecipitation, in vitro kinase activity assays, site-directed mutagenesis of arginine dyad, genetic knockout of TgDJ-1, microneme secretion assay mBio High 28246362
2017 TgCDPK1 and TgCDPK3 contribute to signal quenching (Ca2+ signal dampening) before egress, as revealed by real-time Ca2+ imaging with the GCaMP6 biosensor; their inhibition alters the temporal dynamics of intracellular Ca2+ flux during egress. GCaMP6 genetically encoded Ca2+ biosensor live imaging, pharmacological inhibition of CDPK1 and CDPK3 Cellular microbiology Medium 27781359
2019 TgCDPK1 controls F-actin flux required for motility, invasion, and egress; this flux depends on myosins A and H and is regulated by phosphorylation via PKG and CDPK1, and by methylation via AKMT. This F-actin flux is independent of microneme secretion and persists in the absence of the glideosome-associated connector (GAC). F-actin chromobody live imaging, formin gene disruption, epistasis with PKG and CDPK1 inhibitors, AKMT methyltransferase mutants eLife Medium 30753127
2019 TgCDPK1 and TgCDPK3 mediate negative regulation of dense granule exocytosis by cytosolic Ca2+; elevated Ca2+ suppresses dense granule secretion in a manner contingent on CDPK1 and CDPK3 function, providing reciprocal control with microneme exocytosis. Dense granule secretion assays, Ca2+ manipulation, pharmacological inhibition of CDPK1 and CDPK3 Cellular microbiology Medium 30673152
2020 Thermal proteome profiling of Toxoplasma identified CDPK1 as a target of the antiparasitic compound ENH1; CDPK1 inhibition by ENH1 was confirmed in vitro and in parasites by comparison of sensitive vs. resistant CDPK1 alleles. CDPK1 inhibition explained the egress block, but ENH1 effects on calcium homeostasis and parasite viability were CDPK1-independent, implicating additional targets. Thermal proteome profiling (in situ target identification), in vitro kinase assay, resistant CDPK1 allele comparison, egress assay ACS chemical biology Medium 32597628
2023 Sub-minute resolution phosphoproteomics and bio-orthogonal substrate labeling identified 163 proteins phosphorylated in a CDPK1-dependent manner in T. gondii. Among these, a HOOK activating adaptor is a CDPK1 substrate; CDPK1 kinase activity and HOOK are required for rapid apical trafficking of micronemes as parasites initiate motility. A partially conserved FHF complex (HOOK, FTS homolog, and two parasite-specific proteins) mediates this trafficking, and parasites lacking HOOK or FTS show impaired microneme secretion and a block in host cell invasion. Sub-minute resolution phosphoproteomics, bio-orthogonal kinase substrate labeling (analog-sensitive CDPK1), conditional genetic depletion of HOOK and FTS, microneme secretion assay, invasion assay, live imaging eLife High 37933960
2023 CDPK2A and CDPK1 function in a signaling module upstream of Toxoplasma motility with partial functional redundancy; CDPK2A contributes to microneme discharge, gliding motility, and egress, and epistasis analysis using analog-sensitive alleles and conditional depletion revealed that CDPK2A acts upstream of or in parallel with CDPK1 in the egress/motility pathway. Analog-sensitive kinase alleles (chemical-genetic), conditional protein depletion (auxin-inducible degron), microneme secretion assay, motility assay, egress assay, epistasis analysis mBio Medium 37610220
2006 TgCDPK1 binds a radiolabeled imidazopyridine ligand with sub-nanomolar affinity; mutational analysis of the catalytic site hydrophobic binding pocket (analogous to the gatekeeper residue in PKG) blocks ligand binding, and a compound-refractory CDPK1 mutant (G128Q) overexpressed in transgenic parasites does not reduce susceptibility to the imidazopyridine compound in vivo, indicating that selective inhibition of CDPK1 alone is not responsible for the enhanced anti-parasitic potency of this compound. Radiolabeled ligand binding assay with parasite extracts, site-directed mutagenesis, transgenic overexpression of mutant CDPK1, in vivo parasite growth assays Molecular and biochemical parasitology Medium 16765465
2025 Forward genetic screen using chemical mutagenesis and BKI-1748 resistance selection identified TgMAPKL1 (in addition to TgCDPK1) as a target of BKIs; single mutations in TgMAPKL1 ATP binding site (L162Q) or TgCDPK1 gatekeeper (G128M) each confer 2–6-fold resistance, while combining both mutations yields up to 157-fold resistance, indicating that BKIs dually target both kinases. Chemical mutagenesis forward genetic screen, whole-genome sequencing of resistant clones, site-directed mutagenesis to introduce individual resistance mutations, in vitro kinase inhibition, parasite growth inhibition assays ACS infectious diseases Medium 40407244

Source papers

Stage 0 corpus · 75 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Calcium-dependent protein kinase 1 is an essential regulator of exocytosis in Toxoplasma. Nature 285 20485436
2010 Structures of apicomplexan calcium-dependent protein kinases reveal mechanism of activation by calcium. Nature structural & molecular biology 178 20436473
2012 Distinct signalling pathways control Toxoplasma egress and host-cell invasion. The EMBO journal 167 23149386
2010 Toxoplasma gondii calcium-dependent protein kinase 1 is a target for selective kinase inhibitors. Nature structural & molecular biology 161 20436472
2001 The loss of cytoplasmic potassium upon host cell breakdown triggers egress of Toxoplasma gondii. The Journal of biological chemistry 161 11526113
2001 Toxoplasma gondii attachment to host cells is regulated by a calmodulin-like domain protein kinase. The Journal of biological chemistry 126 11154702
2010 Discovery of Potent and Selective Inhibitors of Calcium-Dependent Protein Kinase 1 (CDPK1) from C. parvum and T. gondii. ACS medicinal chemistry letters 124 21116453
2012 Development of Toxoplasma gondii calcium-dependent protein kinase 1 (TgCDPK1) inhibitors with potent anti-toxoplasma activity. Journal of medicinal chemistry 92 22320388
2006 Anticoccidial kinase inhibitors: identification of protein kinase targets secondary to cGMP-dependent protein kinase. Molecular and biochemical parasitology 87 16765465
2016 Development of an Orally Available and Central Nervous System (CNS) Penetrant Toxoplasma gondii Calcium-Dependent Protein Kinase 1 (TgCDPK1) Inhibitor with Minimal Human Ether-a-go-go-Related Gene (hERG) Activity for the Treatment of Toxoplasmosis. Journal of medicinal chemistry 80 27309760
2015 In Vitro and In Vivo Effects of the Bumped Kinase Inhibitor 1294 in the Related Cyst-Forming Apicomplexans Toxoplasma gondii and Neospora caninum. Antimicrobial agents and chemotherapy 73 26248379
2019 Three F-actin assembly centers regulate organelle inheritance, cell-cell communication and motility in Toxoplasma gondii. eLife 68 30753127
2012 Multiple determinants for selective inhibition of apicomplexan calcium-dependent protein kinase CDPK1. Journal of medicinal chemistry 58 22369268
2013 Optimizing small molecule inhibitors of calcium-dependent protein kinase 1 to prevent infection by Toxoplasma gondii. Journal of medicinal chemistry 57 23470217
2016 Analysis of Noncanonical Calcium-Dependent Protein Kinases in Toxoplasma gondii by Targeted Gene Deletion Using CRISPR/Cas9. Infection and immunity 56 26755159
2017 Inhibition of Calcium Dependent Protein Kinase 1 (CDPK1) by Pyrazolopyrimidine Analogs Decreases Establishment and Reoccurrence of Central Nervous System Disease by Toxoplasma gondii. Journal of medicinal chemistry 54 28933846
2010 Use of the kinase inhibitor analog 1NM-PP1 reveals a role for Toxoplasma gondii CDPK1 in the invasion step. Eukaryotic cell 51 20173034
2014 Potent and selective inhibitors of CDPK1 from T. gondii and C. parvum based on a 5-aminopyrazole-4-carboxamide scaffold. ACS medicinal chemistry letters 50 24494061
2013 Exploiting the unique ATP-binding pocket of toxoplasma calcium-dependent protein kinase 1 to identify its substrates. ACS chemical biology 47 23530747
2015 Allosteric activation of apicomplexan calcium-dependent protein kinases. Proceedings of the National Academy of Sciences of the United States of America 43 26305940
2017 Analysis of Ca2+ mediated signaling regulating Toxoplasma infectivity reveals complex relationships between key molecules. Cellular microbiology 36 27781359
2015 SAR Studies of 5-Aminopyrazole-4-carboxamide Analogues as Potent and Selective Inhibitors of Toxoplasma gondii CDPK1. ACS medicinal chemistry letters 35 26693272
2012 Benzoylbenzimidazole-based selective inhibitors targeting Cryptosporidium parvum and Toxoplasma gondii calcium-dependent protein kinase-1. Bioorganic & medicinal chemistry letters 35 22795629
2014 Protective efficacy of Toxoplasma gondii calcium-dependent protein kinase 1 (TgCDPK1) adjuvated with recombinant IL-15 and IL-21 against experimental toxoplasmosis in mice. BMC infectious diseases 32 25192845
2021 In vitro activity, safety and in vivo efficacy of the novel bumped kinase inhibitor BKI-1748 in non-pregnant and pregnant mice experimentally infected with Neospora caninum tachyzoites and Toxoplasma gondii oocysts. International journal for parasitology. Drugs and drug resistance 31 34030110
2020 Identifying the Target of an Antiparasitic Compound in Toxoplasma Using Thermal Proteome Profiling. ACS chemical biology 30 32597628
2018 Synthesis and evaluation of novel arctigenin derivatives as potential anti-Toxoplasma gondii agents. European journal of medicinal chemistry 30 30237124
2017 The calcium-dependent protein kinase 1 from Toxoplasma gondii as target for structure-based drug design. Parasitology 25 29191253
2013 Identification of mutations in TgMAPK1 of Toxoplasma gondii conferring resistance to 1NM-PP1. International journal for parasitology. Drugs and drug resistance 25 24533298
2022 Protective effect of ginsenoside Rh2 against Toxoplasma gondii infection-induced neuronal injury through binding TgCDPK1 and NLRP3 to inhibit microglial NLRP3 inflammasome signaling pathway. International immunopharmacology 24 36067653
2019 Synthesis and biological evaluation of ursolic acid derivatives bearing triazole moieties as potential anti-Toxoplasma gondii agents. Journal of enzyme inhibition and medicinal chemistry 24 30836795
2015 Co-administration of interleukins 7 and 15 with DNA vaccine improves protective immunity against Toxoplasma gondii. Experimental parasitology 24 26706605
2014 A single mutation in the gatekeeper residue in TgMAPKL-1 restores the inhibitory effect of a bumped kinase inhibitor on the cell cycle. International journal for parasitology. Drugs and drug resistance 22 25941623
2019 Treatment with Bumped Kinase Inhibitor 1294 Is Safe and Leads to Significant Protection against Abortion and Vertical Transmission in Sheep Experimentally Infected with Toxoplasma gondii during Pregnancy. Antimicrobial agents and chemotherapy 21 31061151
2020 Comparative assessment of the effects of bumped kinase inhibitors on early zebrafish embryo development and pregnancy in mice. International journal of antimicrobial agents 18 32707170
2019 Synthesis, in vitro and in vivo biological evaluation of dihydroartemisinin derivatives with potential anti-Toxoplasma gondii agents. Bioorganic chemistry 18 31791681
2019 Perspective on current and emerging drugs in the treatment of acute and chronic toxoplasmosis. Postgraduate medicine 17 31399001
2015 Development of new highly potent imidazo[1,2-b]pyridazines targeting Toxoplasma gondii calcium-dependent protein kinase 1. European journal of medicinal chemistry 17 26479029
2014 Expression of the essential Kinase PfCDPK1 from Plasmodium falciparum in Toxoplasma gondii facilitates the discovery of novel antimalarial drugs. Antimicrobial agents and chemotherapy 17 24550330
2020 Optimizing Pyrazolopyrimidine Inhibitors of Calcium Dependent Protein Kinase 1 for Treatment of Acute and Chronic Toxoplasmosis. Journal of medicinal chemistry 15 32420739
2018 Toxoplasma Calcium-Dependent Protein Kinase 1 Inhibitors: Probing Activity and Resistance Using Cellular Thermal Shift Assays. Antimicrobial agents and chemotherapy 15 29555627
2019 Calcium negatively regulates secretion from dense granules in Toxoplasma gondii. Cellular microbiology 14 30673152
2018 Imidazo[1,2-b]pyridazines targeting Toxoplasma gondii calcium-dependent protein kinase 1 decrease the parasite burden in mice with acute toxoplasmosis. International journal for parasitology 14 29524527
2017 Toxoplasma DJ-1 Regulates Organelle Secretion by a Direct Interaction with Calcium-Dependent Protein Kinase 1. mBio 14 28246362
2023 Analysis of CDPK1 targets identifies a trafficking adaptor complex that regulates microneme exocytosis in Toxoplasma. eLife 13 37933960
2019 Evaluation of protective immunity induced by recombinant calcium-dependent protein kinase 1 (TgCDPK1) protein against acute toxoplasmosis in mice. Microbial pathogenesis 13 31145981
2011 1NM-PP1 treatment of mice infected with Toxoplasma gondii. The Journal of veterinary medical science 13 21685719
2023 CDPK2A and CDPK1 form a signaling module upstream of Toxoplasma motility. mBio 12 37610220
2013 A modular approach to triazole-containing chemical inducers of dimerisation for yeast three-hybrid screening. Molecules (Basel, Switzerland) 11 24064457
2024 An Early Treatment With BKI-1748 Exhibits Full Protection Against Abortion and Congenital Infection in Sheep Experimentally Infected With Toxoplasma gondii. The Journal of infectious diseases 10 37889572
2022 Exploring the Antiparasitic Activity of Tris-1,3,4-Thiadiazoles against Toxoplasma gondii-Infected Mice. Molecules (Basel, Switzerland) 10 35408644
2020 Evaluation of ursolic acid derivatives with potential anti-Toxoplasma gondii activity. Experimental parasitology 9 32569599
2025 Bumped Kinase Inhibitors Inhibit both Toxoplasma gondii MAPKL1 and CDPK1. ACS infectious diseases 7 40407244
2024 Efficacy of the bumped kinase inhibitor BKI-1708 against the cyst-forming apicomplexan parasites Toxoplasma gondii and Neospora caninum in vitro and in experimentally infected mice. International journal for parasitology. Drugs and drug resistance 6 38917582
2017 Novel Molecules To Treat Chronic Central Nervous System Toxoplasmosis. Journal of medicinal chemistry 6 29200288
2024 Immunoinformatics studies and design of a novel multi-epitope peptide vaccine against Toxoplasma gondii based on calcium-dependent protein kinases antigens through an in-silico analysis. Clinical and experimental vaccine research 5 38752002
2024 Isatin-1,2,3-triazole derivatives: Synthesis, molecular docking and evaluation against acute experimental toxoplasmosis. Acta tropica 5 39542154
2023 Photoswitchable Inhibitors to Optically Control Specific Kinase Activity. ACS chemical biology 5 37167414
2021 A Novel Calcium-Dependent Protein Kinase 1 Inhibitor Potently Prevents Toxoplasma gondii Transmission to Foetuses in Mouse. Molecules (Basel, Switzerland) 5 34299478
2025 Chemotherapy against Toxoplasma gondii: A bibliometric analysis of in vitro and mouse model studies (2015-2024). Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 4 40117904
2024 Molecular modelling and experimental validation identified a new therapeutic inhibitor of toxoplasmosis. Computers in biology and medicine 4 39378576
2023 Analysis of CDPK1 targets identifies a trafficking adaptor complex that regulates microneme exocytosis in Toxoplasma. bioRxiv : the preprint server for biology 4 36712004
2025 Nanoformulations for Hydrazones; Synthesis, Characterization, Parasitology, and Histopathology Investigations. ACS omega 3 40454056
2024 Copaifera spp. oleoresins and two isolated compounds (ent-kaurenoic and ent-polyalthic acid) inhibit Toxoplasma gondii growth in vitro. Experimental parasitology 3 38723847
2024 The Intestinal Barrier Protective Effect of Indole Aldehyde Derivatives on Acute Toxoplasma gondii Infection. Molecules (Basel, Switzerland) 3 39519664
2021 In Vitro Anti-Toxoplasma gondii Activity Evaluation of a New Series of Quinazolin-4(3H)-one Derivatives. Chemistry & biodiversity 3 34726832
2020 Discovery of potential Toxoplasma gondii CDPK1 inhibitors with new scaffolds based on the combination of QSAR and scaffold-hopping method with in vitro validation. Chemical biology & drug design 3 31436911
2024 Identification of Coumarin-Chalcone and Coumarin-Pyrazoline Derivatives as Novel Anti-Toxoplasma gondii Agents. Drug design, development and therapy 2 39650850
2025 Quantitative Structure-Activity Relationship Modeling and Molecular Docking Studies of TgCDPK1 Inhibitors in Toxoplasma gondii. MicrobiologyOpen 1 40726092
2023 Computational screening of FDA-approved drugs to identify potential TgDHFR, TgPRS, and TgCDPK1 proteins inhibitors against Toxoplasma gondii. Scientific reports 1 37012275
2026 BKI-1748 confers a high level of protection against ovine congenital toxoplasmosis when administered after IgM seroconversion. Frontiers in cellular and infection microbiology 0 42125495
2026 Lead Optimization of TgCDPK1 Inhibitors for the Treatment of Toxoplasmosis. Journal of medicinal chemistry 0 42231809
2025 Computational Structural Comparison of Toxoplasma gondii CDPK1 and Human BUB1 kinases: Implications for Selective Inhibitor Design. ACS omega 0 40584317
2025 Versatile Imidazole Scaffold with Potent Activity against Multiple Apicomplexan Parasites. ACS infectious diseases 0 40339062
2025 Structure-Based Drug Design of Novel Heterocyclic Scaffolds as TgCDPK1 Inhibitors. ChemMedChem 0 40776603