ArticleCell chemical biology2020
Inhibition of Resistance-Refractory P. falciparum Kinase PKG Delivers Prophylactic, Blood Stage, and Transmission-Blocking Antiplasmodial Activity.
Article in Cell chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Plasmodial Kinase Inhibitors Targeting Malaria: Recent Developments.Molecules (Basel, Switzerland) · 2020Pooled it
- TKL3 regulates blood-stage fitness, male gamete fertility, and transmission-stage development in Plasmodium berghei.PLoS pathogens · 2026Article
- The Human Chk1 Inhibitor CHIR-124 Shows Multistage Activity against the Human Malaria ParasiteACS chemical biology · 2026Article
- An orally available PfPKG inhibitor blocks Plasmodium's infection of the liver.PLoS pathogens · 2026Article
- Article
- Babesia divergens host cell egress is mediated by essential and druggable kinases and proteases.Nature microbiology · 2026Article
- Article
- Computational screening of natural inhibitors against Plasmodium falciparum kinases: Toward novel antimalarial therapies.PloS one · 2026Article
- Targeting Aurora Kinases as Essential Cell-Cycle Regulators to Deliver Multi-Stage Antimalarials Against Plasmodium Falciparum.Angewandte Chemie (International ed. in English) · 2025Article
- An acyclic nucleoside phosphonate effectively blocks the egress of the malaria parasite by inhibiting the synthesis of cyclic GMP.Science advances · 2025Article
- Medicinal Chemistry Progression of Sapanisertib, the Anticancer and DualJournal of medicinal chemistry · 2025Article
- Towards next-generation treatment options to combat Plasmodium falciparum malaria.Nature reviews. Microbiology · 2025Review
- Antimalarial Drug Discovery from Natural and Synthetic Sources.Current medicinal chemistry · 2025Review
- Targeting Malaria's Achilles' Heels: A Review of Plasmodium Life Cycle Vulnerabilities for Drug Discovery.Current topics in medicinal chemistry · 2025Review
- Inhibitors of malaria parasite cyclic nucleotide phosphodiesterases block asexual blood-stage development and mosquito transmission.Science advances · 2024Article
- Structure-based virtual screening against multiple Plasmodium falciparum kinases reveals antimalarial compounds.Molecular diversity · 2024Article
- Systematic in vitro evolution inScience (New York, N.Y.) · 2024Article
- Eliminating malaria transmission requires targeting immature and mature gametocytes through lipoidal uptake of antimalarials.Nature communications · 2024Article
- Repositioning Brusatol as a Transmission Blocker of Malaria Parasites.ACS infectious diseases · 2024Article
- An adaptable, fit-for-purpose screening approach with high-throughput capability to determine speed of action and stage specificity of anti-malarial compounds.Antimicrobial agents and chemotherapy · 2024Article
Corrections and comments
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Authors and funding
31 authors.
Funding
Abstract
The search for antimalarial chemotypes with modes of action unrelated to existing drugs has intensified with the recent failure of first-line therapies across Southeast Asia. Here, we show that the trisubstituted imidazole MMV030084 potently inhibits hepatocyte invasion by Plasmodium sporozoites, merozoite egress from asexual blood stage schizonts, and male gamete exflagellation. Metabolomic, phosphoproteomic, and chemoproteomic studies, validated with conditional knockdown parasites, molecular docking, and recombinant kinase assays, identified cGMP-dependent protein kinase (PKG) as the primary target of MMV030084. PKG is known to play essential roles in Plasmodium invasion of and egress from host cells, matching MMV030084's activity profile. Resistance selections and gene editing identified tyrosine kinase-like protein 3 as a low-level resistance mediator for PKG inhibitors, while PKG itself never mutated under pressure. These studies highlight PKG as a resistance-refractory antimalarial target throughout the Plasmodium life cycle and promote MMV030084 as a promising Plasmodium PKG-targeting chemotype.
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Registered trials
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.