ArticleMalaria journal2020
An in vitro toolbox to accelerate anti-malarial drug discovery and development.
Article in Malaria journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 158 citations in OpenAlex.
- Unanticipated CNS Safety Signal in a Placebo-Controlled, Randomized Trial of Co-Administered Atovaquone-Proguanil and Amodiaquine.Clinical pharmacology and therapeutics · 2022Trial
- Examination of Coligands in Mefloquine-Metal Complexes Reveals the Structural Determinants of Activity againstJournal of medicinal chemistry · 2026Article
- Integrative preclinical strategy for pharmacokinetic profiling and candidate selection of 3-hydroxypropanamidines: a promising antimalarial class.Malaria journal · 2026Article
- Lactobionic Acid as a Biocompatibility Switch: Physicochemical and Biological Characterization of Copper(II)-Primaquine Complexes.Bioinorganic chemistry and applications · 2026Article
- Physiologically based pharmacokinetic modeling of tafenoquine and evaluation of transporter-mediated drug-drug interactions.Frontiers in pharmacology · 2026Article
- Importance of Lysosomal Trapping and Plasmodium Parasite Infection on the Pharmacokinetics of Pyronaridine: A Physiologically Based Pharmacokinetic Model-Based Study.Clinical pharmacokinetics · 2025Article
- Structure-Activity Relationship of Antischistosomal Aryl Hydantoin (AR102).Journal of medicinal chemistry · 2025Article
- Structure-Activity Relationships of 3-Hydroxypropanamidines (HPAs) with Potent In Vivo Antimalarial Activity.Journal of medicinal chemistry · 2025Article
- Indirect Modeling of Post-Prandial Intestinal Lymphatic Uptake of Halofantrine Using PBPK Approaches: Limitations and Implications.Pharmaceutics · 2025Article
- Co-CulturingAntibiotics (Basel, Switzerland) · 2025Article
- Identifying a next-generation antimalarial trioxolane in a landscape of artemisinin partial resistance.Science advances · 2025Article
- Article
- The Importance of Murine Models in Determining In Vivo Pharmacokinetics, Safety, and Efficacy in Antimalarial Drug Discovery.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Structure-Based Discovery and Development of Highly Potent Dihydroorotate Dehydrogenase Inhibitors for Malaria Chemoprevention.Journal of medicinal chemistry · 2025Article
- TKK130 is a 3-Hydroxy-Propanamidine (HPA) with Potent AntimalarialJournal of medicinal chemistry · 2025Article
- A Comprehensive Review on the Pharmacokinetics and Bioanalysis of Piperaquine.Current drug metabolism · 2025Review
- Single-Dose Drug Development Candidate for Schistosomiasis.ACS infectious diseases · 2024Article
- Medium-Ring Keto Bislactams with Antischistosomal Activity.Journal of medicinal chemistry · 2024Article
- Synthesis and In Vivo Profiling of Desymmetrized Antimalarial Trioxolanes with Diverse Carbamate Side Chains.ACS medicinal chemistry letters · 2024Article
- Dose-fractionation studies of aAntimicrobial agents and chemotherapy · 2024Article
Corrections and comments
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Authors and funding
23 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundModelling and simulation are being increasingly utilized to support the discovery and development of new anti-malarial drugs. These approaches require reliable in vitro data for physicochemical properties, permeability, binding, intrinsic clearance and cytochrome P450 inhibition. This work was conducted to generate an in vitro data toolbox using standardized methods for a set of 45 anti-malarial drugs and to assess changes in physicochemical properties in relation to changing target product and candidate profiles.
methodsIonization constants were determined by potentiometric titration and partition coefficients were measured using a shake-flask method. Solubility was assessed in biorelevant media and permeability coefficients and efflux ratios were determined using Caco-2 cell monolayers. Binding to plasma and media proteins was measured using either ultracentrifugation or rapid equilibrium dialysis. Metabolic stability and cytochrome P450 inhibition were assessed using human liver microsomes. Sample analysis was conducted by LC-MS/MS.
resultsBoth solubility and fraction unbound decreased, and permeability and unbound intrinsic clearance increased, with increasing Log D
conclusionsThis is the first data set to describe in vitro properties for 45 legacy and development anti-malarial drugs. The studies identified several practical methodological issues common to many of the more lipophilic compounds and highlighted areas which require more work to customize experimental conditions for compounds being designed to meet the new target product profiles. The dataset will be a valuable tool for malaria researchers aiming to develop PBPK models for the prediction of human PK properties and/or drug-drug interactions. Furthermore, generation of this comprehensive data set within a single laboratory allows direct comparison of properties across a large dataset and evaluation of changing property trends that have occurred over time with changing target product and candidate profiles.
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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.