Article in ChemMedChem, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.4field-weighted citation impact, top 19% 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
5 citing papers in PubMed, 16 citations in OpenAlex.
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
13 authors at 2 institutions in 2 countries.
Niklas G JohanssonDrug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5 E), 00014, Helsinki, Finland.ORCID 0000-0002-8226-4813
Loïc DreanoDrug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5 E), 00014, Helsinki, Finland.
Keni VidilaserisDepartment of Biosciences, Division of Biochemistry, University of Helsinki, P.O. Box 56 (Viikinkaari 9), 00014, Helsinki, Finland.ORCID 0000-0002-6453-6600
Ayman KhattabMalaria Research Laboratory, Translational Immunology Research Program, Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, P.O. Box 21 (Haartmaninkatu 3), 00014, Helsinki, Finland.ORCID 0000-0002-3980-8379
Jianing LiuDepartment of Biosciences, Division of Biochemistry, University of Helsinki, P.O. Box 56 (Viikinkaari 9), 00014, Helsinki, Finland.
Arthur LasbleizDrug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5 E), 00014, Helsinki, Finland.
Orquidea RibeiroDepartment of Biosciences, Division of Biochemistry, University of Helsinki, P.O. Box 56 (Viikinkaari 9), 00014, Helsinki, Finland.ORCID 0000-0003-0746-6666
Alexandros KiriazisDrug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5 E), 00014, Helsinki, Finland.ORCID 0000-0002-2488-1506
Gustav Boije Af GennäsDrug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5 E), 00014, Helsinki, Finland.ORCID 0000-0002-0099-6085
Seppo MeriMalaria Research Laboratory, Translational Immunology Research Program, Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, P.O. Box 21 (Haartmaninkatu 3), 00014, Helsinki, Finland.ORCID 0000-0001-9142-501X
Adrian GoldmanDepartment of Biosciences, Division of Biochemistry, University of Helsinki, P.O. Box 56 (Viikinkaari 9), 00014, Helsinki, Finland.ORCID 0000-0001-8032-9700
Jari Yli-KauhaluomaDrug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5 E), 00014, Helsinki, Finland.ORCID 0000-0003-0370-7653
Henri XhaardDrug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5 E), 00014, Helsinki, Finland.ORCID 0000-0002-3000-7858
University of Helsinki · FIUniversity of Leeds · GB
Funding
Academy of Finland 1322609Academy of Finland 1323237Academy of Finland 265481Academy of Finland 308105Academy of Finland 310297Biotechnology and Biological Sciences Research Council BB/M021610/1
6 · The paper itself
Abstract
Inhibition of membrane-bound pyrophosphatase (mPPase) with small molecules offer a new approach in the fight against pathogenic protozoan parasites. mPPases are absent in humans, but essential for many protists as they couple pyrophosphate hydrolysis to the active transport of protons or sodium ions across acidocalcisomal membranes. So far, only few nonphosphorus inhibitors have been reported. Here, we explore the chemical space around previous hits using a combination of screening and synthetic medicinal chemistry, identifying compounds with low micromolar inhibitory activities in the Thermotoga maritima mPPase test system. We furthermore provide early structure-activity relationships around a new scaffold having a pyrazolo[1,5-a]pyrimidine core. The most promising pyrazolo[1,5-a]pyrimidine congener was further investigated and found to inhibit Plasmodium falciparum mPPase in membranes as well as the growth of P. falciparum in an ex vivo survival assay.
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.
Exploration of Pyrazolo[1,5-a]pyrimidines as Membrane-Bound Pyrophosphatase Inhibitors. · full record | OpenQuestion