A5006734746- Drug Transport and Resistance Mechanisms
- Drug Solubulity and Delivery Systems
- Pharmaceutical studies and practices
- Malaria Research and Control
- Advanced Drug Delivery Systems
- Pharmacogenetics and Drug Metabolism
- Analytical Chemistry and Chromatography
- Computational Drug Discovery Methods
- Antibiotics Pharmacokinetics and Efficacy
- Diet and metabolism studies
- Analytical Methods in Pharmaceuticals
- Ion Transport and Channel Regulation
- HIV/AIDS drug development and treatment
- Crystallization and Solubility Studies
- Protein purification and stability
- Receptor Mechanisms and Signaling
- Pharmacological Effects and Toxicity Studies
- Synthesis and Catalytic Reactions
- Epilepsy research and treatment
- Biochemical and Molecular Research
- Lipid Membrane Structure and Behavior
- Anesthesia and Pain Management
- Pharmaceutical Practices and Patient Outcomes
- Pneumocystis jirovecii pneumonia detection and treatment
- Gastrointestinal motility and disorders
Monash University
2011-2021
NAACP Legal Defense and Educational Fund
1997-2017
Institut des Hautes Études Scientifiques
2016
Servier (France)
2016
Pharmaceutical Biotechnology (Czechia)
2008-2013
Pfizer (United States)
2013
The University of Texas Southwestern Medical Center
2009
Australian Regenerative Medicine Institute
2004-2009
Roche (Switzerland)
2005
Swiss Tropical and Public Health Institute
2005
Ozonide OZ439 is a synthetic peroxide antimalarial drug candidate designed to provide single-dose oral cure in humans. has successfully completed Phase I clinical trials, where it was shown be safe at doses up 1,600 mg and currently undergoing IIa trials malaria patients. Herein, we describe the discovery of exceptional pharmacokinetic properties that led its selection as development candidate. In vitro, fast-acting against all asexual erythrocytic Plasmodium falciparum stages with IC 50...
Drug therapy is the mainstay of antimalarial therapy, yet current drugs are threatened by development resistance. In an effort to identify new potential antimalarials, we have undertaken a lead optimization program around our previously identified triazolopyrimidine-based series Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors. The X-ray structure PfDHODH was used inform medicinal chemistry allowing identification potent and selective inhibitor (DSM265) that acts...
Malarial dihydrofolate reductase (DHFR) is the target of antifolate antimalarial drugs such as pyrimethamine and cycloguanil, clinical efficacy which have been compromised by resistance arising through mutations at various sites on enzyme. Here, we describe use cocrystal structures with inhibitors substrates, along pharmacokinetic profiling for design, characterization, preclinical development a selective, highly efficacious, orally available drug candidate that potently inhibits both...
The assumption that drug repurposing efficiently delivers new drugs ignores the realities of development required to achieve regulatory approval.
Abstract An evaluation of the in-vitro digestion profile and phase behaviour common formulation lipids Miglyol 812 (medium chain triglyceride, MCT), Capmul MCM (C8/C10 monoglyceride/diglyceride mixture), soybean oil (long LCT) Maisine 35-1 (C18 is described. Experiments were conducted using titrimetric, high-performance thin-layer chromatographic (HPTLC) ultracentrifugational techniques under model fasted post-prandial intestinal conditions. The rate extent medium was greater than...
Plasmodium falciparum causes 1−2 million deaths annually. Yet current drug therapies are compromised by resistance. We previously described potent and selective triazolopyrimidine-based inhibitors of P. dihydroorotate dehydrogenase (PfDHODH) that inhibited parasite growth in vitro; however, they showed no activity vivo. Here we show lack efficacy against berghei mice resulted from a combination poor plasma exposure reduced potency DHODH. For compounds containing naphthyl (DSM1) or...