A5043247022- Research on Leishmaniasis Studies
- Trypanosoma species research and implications
- Malaria Research and Control
- Synthesis and Catalytic Reactions
- Synthesis and biological activity
- Mycobacterium research and diagnosis
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Tuberculosis Research and Epidemiology
- Computational Drug Discovery Methods
- Antibiotics Pharmacokinetics and Efficacy
- Carcinogens and Genotoxicity Assessment
- S100 Proteins and Annexins
- Cancer therapeutics and mechanisms
- Molecular Biology Techniques and Applications
- Biosimilars and Bioanalytical Methods
- Nanoparticles: synthesis and applications
- Viral Infectious Diseases and Gene Expression in Insects
- Erythrocyte Function and Pathophysiology
- Cardiac electrophysiology and arrhythmias
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- Air Quality and Health Impacts
- Cancer, Stress, Anesthesia, and Immune Response
- Synthesis and Biological Evaluation
Age UK
2024
GlaxoSmithKline (United Kingdom)
2009-2023
University of Hertfordshire
2022
University of Liverpool
2009
Liverpool School of Tropical Medicine
2009
This first-time-in-human (FTIH) study evaluated the safety, tolerability, pharmacokinetics, and food effect of single repeat oral doses GSK3036656, a leucyl-tRNA synthetase inhibitor. In part A, GSK3036656 5 mg (fed fasted), 15 mg, 25 placebo were administered. B, administered for 14 days once daily. showed dose-proportional increase following single-dose administration after dosing days. The maximum concentration drug in serum (Cmax) area under concentration-time curve from 0 h to end...
N-tert-Butyl isoquine (4) (GSK369796) is a 4-aminoquinoline drug candidate selected and developed as part of public−private partnership between academics at Liverpool, MMV, GSK pharmaceuticals. This molecule was rationally designed based on chemical, toxicological, pharmacokinetic, pharmacodynamic considerations excellent activity against Plasmodium falciparum in vitro rodent malaria parasites vivo. The optimized chemistry delivered this novel synthetic quinoline two-step procedure from...
The sensitivity of Mycobacterium tuberculosis , the pathogen that causes (TB), to antibiotic prodrugs is dependent on efficacy activation process transforms into their active antibacterial moieties. Various oxidases M. have potential activate prodrug ethionamide. Here, we used medicinal chemistry coupled with a phenotypic assay select N-acylated 4-phenylpiperidine compound series. lead compound, SMARt751, interacted transcriptional regulator VirS which regulates mymA operon encoding...
On the basis of a mechanistic understanding toxicity 4-aminoquinoline amodiaquine (1b), three series analogues have been prepared where 4-aminophenol "metabolic alert" has modified by replacement 4′-hydroxy group with hydrogen, fluorine, or chlorine atom. Following antimalarial assessment and studies on mechanism action, two candidates were selected for detailed ADME in vitro vivo toxicological assessment. 4′-Fluoro-N-tert-butylamodiaquine (2k) was subsequently identified as candidate...
The leishmaniases are diseases that affect millions of people across the world, in particular visceral leishmaniasis (VL) which is fatal unless treated. Current standard care for VL suffers from multiple issues and there a limited pipeline new candidate drugs. As such, clear unmet medical need to identify treatments. This paper describes optimization phenotypic hit against Leishmania donovani, major causative organism VL. key challenges were balance solubility metabolic stability while...
GSK3191607, a novel inhibitor of the Plasmodium falciparum ATP4 (PfATP4) pathway, is being considered for development in humans. However, key problem encountered during preclinical evaluation compound was its inconsistent pharmacokinetic (PK) profile across species (mouse, rat and dog), which prevented reliable prediction PK parameters humans precluded well-founded assessment potential clinical compound. Therefore, an open-label microdose (100 μg, six subjects) first time study conducted to...