mefloquine / Generic mfg. - LARVOL DELTA

FDA-approved drug library screen identifies antidepressants, antimicrobials, anti-COPD, and anti-CVD agents as blockers of NLRP3 inflammasome and sepsis in a sex-dependent manner. (PubMed, bioRxiv) - "Various classes of drugs, such as antidepressants (Fluoxetine, Duloxetine), antihypertensives (Irbesartan, amlodipine, nebivolol), antidiabetics (Rosiglitazone), β-adrenergic agonists (Salmeterol), antimalarials (Mefloquine), antifungals (Azoles, ciclopirox), and antivirals (Saquinavir, Remdesivir), were identified as potent blockers of either priming or assembly of NLRP3 inflammasome. Mice treated with LPS-priming blockers showed a sex-specific increase in survival rate in the mouse model of LPS-induced mortality, validating the in vitro screen. Further studies in primary human cells and in vivo disease models are needed to assess the repurposing and therapeutic relevance of identified drugs."

FDA event • Journal • Alzheimer's Disease • Asthma • Chronic Obstructive Pulmonary Disease • CNS Disorders • Diabetes • Genetic Disorders • Gout • Immunology • Infectious Disease • Inflammatory Arthritis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Movement Disorders • Novel Coronavirus Disease • Obesity • Parkinson's Disease • Pulmonary Disease • Respiratory Diseases • Rheumatology • Septic Shock • NLRP3

4-Aminoquinolines block heme iron reactivity and interfere with artemisinin action. (PubMed, Elife) - "We found that chloroquine (CQ), piperaquine (PPQ), and amodiaquine substantially antagonize dihydroartemisinin (DHA), the active metabolite of artemisinins. Finally, we probed beyond traditional ACTs, evaluating interactions of the proposed triple ACT, DHA-PPQ-mefloquine, as well as OZ439-quinoline combinations, which were all found to be antagonistic. Collectively, these in vitro data suggest that peroxide-quinolines may have liabilities as combination therapies."

Journal • Infectious Disease • Malaria

Examination of Coligands in Mefloquine-Metal Complexes Reveals the Structural Determinants of Activity against Plasmodium falciparum and Schistosoma mansoni. (PubMed, J Med Chem) - "Notably, despite being isostructural, Pd complexes differed from their Pt counterparts in their ligand dissociation behavior. The current work establishes a new structural framework for developing metal-based antiparasitic agents capable of selectively targeting essential parasite biochemical pathways while sparing mammalian cells."

Journal

A network-driven computational framework for identifying FDA-approved drug repurposing across heterogeneous brain cancers. (PubMed, Front Mol Biosci) - "As a result, three repurposed drugs were identified as priorities: (i) mefloquine (reference drug: vorasidenib citrate), (ii) clofibric acid (reference drug: carmustine), and armillarisin A (reference drug: lomustine). These results also suggest repurposing candidates for synergistic combinations across different brain tumors. The two applications developed in this work are freely accessible and in the public domain at https://assay.smallmoles.com/escorwin."

FDA event • Heterogeneity • Journal • Brain Cancer • Oncology • Solid Tumor • BRAF • CDK1 • EGFR • KDR • PDGFRA • TERT • TP53

Evaluation of the Efficacy of Anthelmintic Drugs Against Trichinella spiralis Larvae. (PubMed, Antibiotics (Basel)) - "Background: Albendazole, mebendazole, and ivermectin are effective against adult Trichinella spiralis but show limited efficacy against encapsulated muscle stage larvae... Seven antiparasitic drugs, albendazole (ABZ), miltefosine (MLT), ivermectin (IVM), tribendimidine (TBD), praziquantel (PZQ), artesunate (ART), and mefloquine (MEQ), were evaluated for in vitro activity against T. spiralis muscle larvae...In vivo, TBD treatment significantly reduced larval burdens in diaphragm and gastrocnemius muscles and was associated with reduced collagen capsule thickness, inflammation, and fibrosis compared with ABZ-treated controls. This study validated an assay for quantitative evaluation of T. spiralis muscle larvae and demonstrates robust in vitro and in vivo activity of TBD against this stage."

Journal • Fibrosis • Immunology • Inflammation

Imported Malaria in a Malaria-Free Region: A Retrospective Analysis of Epidemiological, Clinical, and Therapeutic Patterns in Tizi-Ouzou, Algeria (2018-2024). (PubMed, J Vector Borne Dis) - "Mefloquine was the most prescribed treatment (71.4%). Imported malaria in Tizi-Ouzou is characterized by P. falciparum predominance, absence of chemoprophylaxis, short post-travel incubation, and travel-linked seasonality. Strengthening pre-travel counseling, improving prophylaxis, uptake, and enhancing clinician awareness are crucial to prevent severe disease and reduce the risk of malaria reintroduction in Algeria."

Journal • Retrospective data • Hematological Disorders • Infectious Disease • Malaria • Thrombocytopenia

Double Salts and Racemate in Mefloquine-Ibuprofen and Mefloquine-Ketoprofen Systems. A Structural and Thermochemical Analysis. (PubMed, Chirality) - "Using a drug-drug approach, we have investigated the crystallization behavior of Mefloquine (Mf), a racemic antimalarial drug, in combination with enantiopure (S)-ibuprofen and (S)-ketoprofen, as well as their racemic forms. On the other hand, the racemate with ketoprofen and the double salt with ibuprofen are the most soluble structures, suggesting that they are more stable systems than their counterparts. These findings support the view that double salt formation in such systems results from structural mimicry of racemates, emphasizing the challenges of predictable enantiomeric resolution and the importance of understanding structure-property relationships in chiral crystallization."

Journal • Infectious Disease

Pharmacokinetic and pharmacodynamic modeling of anti-plasmodial drugs mefloquine plus artesunate: insights on translational application. (PubMed, Antimicrob Agents Chemother) - "In contrast, AS monotherapy exhibited a rapid initial parasite clearance, but this was followed by a parasite recrudescence. These findings underscore the value of combination therapy and highlight the utility of integrated PK/PD modeling to inform antimalarial treatment optimization in preclinical studies and support translational application."

Journal • PK/PD data • Infectious Disease

Residual antimalarial drug concentrations before treatment in malaria patients in Asia and Africa: A systematic review and meta-analysis depicting its implication for drug pressure. (PubMed, Parasite Epidemiol Control) - "Subgroup analysis (per drug type) showed that the pooled proportion estimates of malaria patients with pre-treatment drug levels were higher for Chloroquine and Lumefantrine (55.0%, 95% CI 26.0%-82.0% & 34.0%, 95% CI 10.0%-63.0%, respectively), contributed by most studies from Africa. With regard to mefloquine, the proportion estimates were 10.0%, 95% CI 01.0%-26.0% contributed by most studies from Asia. The substantial pooled proportions of malaria patients with pre-treatment drug levels imply the existence of drug pressure, which is potential for the development of antimalarial drug resistance."

Journal • Retrospective data • Review • Infectious Disease • Malaria

Electrical Synapses Contribute to Sleep-Dependent Declarative Memory Retention. (PubMed, Eur J Neurosci) - "In supplemental experiments in rats, mefloquine administered i.p. at escalating doses of 20 and 40 mg/kg did not alter hippocampal sharp-wave/ripple activity, a prominent mechanism of hippocampal memory replay. While mefloquine effects beyond gap junctions in the present experiments cannot be fully excluded, we conclude that electrical coupling enhances the oscillatory coordination between sleep spindles and slow oscillations and, thereby, supports systems memory consolidation."

Journal • Infectious Disease

A common DNA deletion altering the 3'UTR of mdr1 is associated with reduced mefloquine susceptibility in P. vivax parasites from Cambodian patients. (PubMed, Nat Commun) - "In Cambodian isolates, the deletion was significantly associated with a higher level of mdr1 mRNA, a lower ex vivo susceptibility to mefloquine, and increased in frequency in Cambodia since the introduction of mefloquine as ACT partner drug. Overall, these findings indicate that a common deletion of a non-coding sequence affects the transcription, stability, or translation of mdr1 in P. vivax parasites and could mediate reduced susceptibility to antimalarial drug(s) currently used for the treatment of uncomplicated vivax malaria."

Journal • Infectious Disease • Malaria • ABCB1

Innovative application of mefloquine and Methacycline in combating Tet(X3/X4)-positive Escherichia coli infections. (PubMed, BMC Microbiol) - "The advent and global spread of plasmid-carried resistance genes, including the tigecycline resistance gene tet(X3/X4) and the colistin resistance gene mcr-1, present a substantial threat to public health that requires immediate resolution. This study successfully screened and identified commercial anti-parasitic drugs that efficiently inhibit Tet(X4) enzyme activity (IC50 = 79.42 µg/mL), revealing that mefloquine exhibited a synergistic antibacterial effect with tetracyclines against tet(X3/X4)-positive bacteria (FIC < 0.5) and an additive effect with tetracyclines against tet(X3/X4)-negative bacteria (0.5 < FIC < 1, excluding minocycline)...Furthermore, in the mouse infection model of E. coli 47EC, the combination of methacycline and mefloquine, demonstrated significant therapeutic advantages, as evidenced by an increased survival rate (from 20.00% to 80.00%), decreased sepsis score, and decreased bacterial load. Our work is the first to reveal that..."

Journal • Infectious Disease • Septic Shock

Structural basis of PANX1 permeation and positive modulation by mefloquine. (PubMed, Nat Commun) - "We also identify mefloquine as a positive modulator of PANX1 that binds near the side tunnel to control ion flow through this pathway. Together, these findings define the structural principles underlying PANX1 permeation and modulation."

Journal

Tolerance of Plasmodium falciparum mefloquine-resistant clinical isolates to mefloquine-piperaquine with implications for triple artemisinin-based combination therapies. (PubMed, Nat Commun) - "Mechanistic investigations reveal that MQ inhibits PPQ accumulation in a dose-dependent manner, providing a functional explanation for the compromised efficacy of the combination. These findings demonstrate that MQ resistance alone can undermine MQ-PPQ TACT efficacy, calling into question the strategic rationale of this combination and underscoring the need for alternative regimens with a lower risk of resistance selection."

Journal • ABCB1

Niosomal mefloquine and cisplatin in breast cancer: comparative effects on apoptosis and angiogenesis via in vitro and in silico analysis. (PubMed, BMC Cancer) - "The niosomal formulation of MEF synergistically enhances CIS efficacy by promoting apoptosis, and suppressing angiogenesis in TNBC. These findings highlight NMEF as a promising chemosensitizer to overcome cisplatin resistance. Future studies should focus on in vivo validation and clinical translation."

IO biomarker • Journal • Preclinical • Breast Cancer • Infectious Disease • Oncology • Solid Tumor • Triple Negative Breast Cancer • BAX • BCL2 • CASP3 • KDR

A Case of Cerebellar-Onset Progressive Multifocal Leukoencephalopathy (PML) Associated with Hepatitis B-related Liver Cirrhosis. (PubMed, Intern Med) - "Treatment with mefloquine and mirtazapine resulted in viral clearance from the cerebrospinal fluid (CSF) and clinical stabilization. This case highlights that crescent-shaped cerebellar lesions should raise suspicion of PML, even in patients without severe immunodeficiency."

Journal • Ataxia • CNS Disorders • Fibrosis • Gastroenterology • Hepatitis B • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis • Movement Disorders • Rare Diseases

Transplacental Transfer of Lumefantrine, Mefloquine, and Piperaquine: A Comparison of Concentrations in Mothers, Neonates, and Cord Blood. (PubMed, Clin Infect Dis) - "Antimalarial drugs crossed the placenta variably. Neonatal concentrations ranged from less than half (lumefantrine, mefloquine) to near maternal equivalence (piperaquine). Collection of neonatal capillary samples at birth should be considered in future studies.SummaryWe compared antimalarial blood concentrations in mothers, neonates, and cords. Neonatal drug concentrations ranged from near maternal equivalence (piperaquine) to less than half (lumefantrine, mefloquine). Cord concentrations may underestimate neonatal exposure. Future studies should consider neonatal capillary sampling."

Journal • Infectious Disease • Malaria

Targeting Glycolysis with 2-Deoxy-D-Glucose and Lysosomal Integrity with L-Leucyl-L-Leucine Methyl Ester as Antimelanoma Strategy. (PubMed, Pharmaceutics) - "Background/Objectives: Melanoma cells enhance glycolysis and expand lysosomes to support energy metabolism, proliferation, and metastasis. However, mefloquine and siramesine induced stronger LMP in A375 cells than in fibroblasts and showed melanoma-selective toxicity when combined with 2DG. 2DG-mediated glycolysis inhibition in combination with lysosomal destabilization induced by mefloquine and siramesine, but not with non-selectively toxic LLOMe, may be promising antimelanoma strategy."

Journal • Melanoma • Metabolic Disorders • Oncology • Solid Tumor • CTSC • CTSS • HK2

Identification of a novel locus associated with decreased susceptibility of Plasmodium falciparum to lumefantrine and artemisinin in Uganda (ASTMH 2025) - "The most common artemisinin-based combination (ACT), artemether-lumenantrine, is threatened in Uganda, where multiple artemisinin partial resistance (ART-R) mutations in Kelch13 (K13), including the C469Y and A675V mutations, are spreading, and decreasing lumefantrine (LUM) susceptibility has been demonstrated...PIN-carrying isolates showed significantly decreased ex vivo susceptibility to LUM, mefloquine and dihydroartemisinin (DHA) compared to WT (P<0.0001 for each drug). The newly identified PIN haplotype represents a candidate marker for decreased susceptibility to DHA and/or LUM. Its rapid spread in Uganda underscores the importance of evaluating its distribution and role in the emergence of ART-R elsewhere in East Africa."

Late-breaking abstract • Infectious Disease

Field-deployable targeted nanopore sequencing to assess molecular markers of anti-malarial resistance, clonality, and Plasmodium falciparum hrp2/3 gene deletions in western Kenya (ASTMH 2025) - "We implemented a rapid amplicon nanopore sequencing panel for crt (chloroquine), dhfr (pyrimethamine), dhps (sulfadoxine), kelch13 (artemisinin), mdr1 (mefloquine), ama1 (complexity of infection), and hrp2/3 (RDT) genes...Nearly all, 97.2% (139/145) samples exhibited the quintuple dhfr (N51I, C59R, S108N) and dhps (A437G, K540E) genotype associated with sulfadoxine-pyrimethamine resistance...Among the 34 samples with potential hrp2/3 gene deletion based on RDT results, none had hrp2/3 gene deletions by nanopore sequencing. Nanopore sequencing is a robust methodology which can be carried out locally, providing powerful information to inform programming."

Biomarker • Infectious Disease • Malaria • ABCB1 • DHFR

Mining for Malaria: Delayed Diagnosis and Prolonged Parasitemia in a Active Duty Servicemember (ASTMH 2025) - "He took doxycycline prophylaxis for the first eight months but switched to mefloquine for less frequent dosing and reported complete adherence. The reason for his delayed parasitemia clearance is unclear. This case highlights the pitfalls of relying on RDT for the diagnosis of malaria and the potential complexities the management of delayed parasitemia clearance and possible artemisinin resistance."

Anemia • Fatigue • Hematological Disorders • Infectious Disease • Influenza • Malaria • Musculoskeletal Pain • Novel Coronavirus Disease • Respiratory Diseases

Genomic Epidemiological Analysis of Antimalarial Drug Resistance Evolution in Mali, 2007-2017 (ASTMH 2025) - "Analyzed haplotypes included mutations in the Pfdhfr and Pfdhps genes, critical for resistance to Sulfadoxine-Pyrimethamine (SP). Chloroquine resistance has notably decreased. No resistance to piperaquine, mefloquine, or artemisinin was detected, indicating their continued efficacy."

Clinical • Infectious Disease • Malaria • ABCB1 • DHFR

Field-deployable targeted nanopore sequencing to assess molecular markers of anti-malarial resistance, clonality, and Plasmodium falciparum hrp2/3 gene deletions in western Kenya (ASTMH 2025) - "We implemented a rapid amplicon nanopore sequencing panel for crt (chloroquine), dhfr (pyrimethamine), dhps (sulfadoxine), kelch13 (artemisinin), mdr1 (mefloquine), ama1 (complexity of infection), and hrp2/3 (RDT) genes...Nearly all, 97.2% (139/145) samples exhibited the quintuple dhfr (N51I, C59R, S108N) and dhps (A437G, K540E) genotype associated with sulfadoxine-pyrimethamine resistance...Among the 34 samples with potential hrp2/3 gene deletion based on RDT results, none had hrp2/3 gene deletions by nanopore sequencing. Nanopore sequencing is a robust methodology which can be carried out locally, providing powerful information to inform programming."

Biomarker • Infectious Disease • Malaria • ABCB1 • DHFR

Natural in vitro susceptibility of Plasmodium falciparum to pyronaridine over 2009-2023 in French Guiana (ASTMH 2025) - "Currently, only artemether-lumefantrine remains effective in the region...Correlation between pyronaridine and other aminoquinoline derivatives including chloroquine, monodesethylamodiaquine, and mefloquine was assessed (r2=0.01; r2=0.04; r2=0.11, respectively), but no cross-resistance was found...However, the synonymous mutation PfMDR1S1034S, observed in 63% of French Guiana isolates, was associated with decreased pyronaridine susceptibility (p < 0.0001). The findings of this study suggest that artesunate-pyronaridine could be a new treatment alternative for P. falciparum in the Amazon region."

Preclinical • Infectious Disease • Malaria • ABCB1

Application of GC3,a locus read coverage assessment tool, and machine learning to predict copy number variations of pfmdr1, plasmepsin-2, and plasmepsin-3 among Plasmodium falciparum strains (ASTMH 2025) - "Specifically, we are focusing on CNVs at the Plasmodium falciparum (Pf) multidrug resistant protein 1 (Pfmdr1), plasmepsin-2 (pm2) and plasmepsin-3 (pm3) genes, which are associated with resistance to partner drugs used in some artemisinin-based combination therapies (ACTs), including mefloquine and piperaquine...Follow up analysis aims to expand our sample set to ~700 publicly available WGS samples from 13 malaria endemic countries in South America, Africa and Asia, and apply machine learning models to improve the prediction of CNVs. By expanding on the previous application of GC3 to identify CNVs, results aim to demonstrate the feasibility of applying bioinformatics to automate accurate prediction and measure the prevalence of CNVs associated with drug resistance using WGS data."

Machine learning • Infectious Disease • Malaria • ABCB1