A5001249714- HIV/AIDS drug development and treatment
- HIV Research and Treatment
- Research on Leishmaniasis Studies
- HIV/AIDS Research and Interventions
- Trypanosoma species research and implications
- Advanced biosensing and bioanalysis techniques
- Biochemical and Molecular Research
- Genetics, Bioinformatics, and Biomedical Research
- Metabolism and Genetic Disorders
- SARS-CoV-2 detection and testing
- SARS-CoV-2 and COVID-19 Research
- Innovative Microfluidic and Catalytic Techniques Innovation
- Advanced Biosensing Techniques and Applications
- Tuberculosis Research and Epidemiology
- Cancer therapeutics and mechanisms
- Mycobacterium research and diagnosis
- Cell Image Analysis Techniques
- Synthesis and Biological Evaluation
- Quinazolinone synthesis and applications
- Hepatitis C virus research
- Monoclonal and Polyclonal Antibodies Research
- RNA Interference and Gene Delivery
- Computational Drug Discovery Methods
- thermodynamics and calorimetric analyses
- Caveolin-1 and cellular processes
Institut Pasteur Korea
2009-2022
McMaster University
1998-2007
Drugs currently available for leishmaniasis treatment often show parasite resistance, highly toxic side effects and prohibitive costs commonly incompatible with patients from the tropical endemic countries. In this sense, there is an urgent need new drugs as a solution neglected disease. Here we development implementation of automated high-throughput viability screening assay discovery against Leishmania. Assay validation was done Leishmania promastigote forms, including 4,000 compounds...
Leishmaniasis is a tropical disease threatening 350 million people from endemic regions. The available drugs for treatment are inadequate, with limitations such as serious side effects, parasite resistance or high cost. Driven by this need new drugs, we developed high-content, high-throughput image-based screening assay targeting the intracellular amastigote stage of different species Leishmania in infected human macrophages. vitro infection protocol was adapted to 384-well-plate format,...
We used quantitative immunogold electron microscopy and biochemical analysis to evaluate the subcellular distribution of Hsp60 in rat tissues. Western blot analysis, employing both monoclonal polyclonal antibodies raised against mammalian Hsp60, shows that only a single 60-kD protein is reactive with brain, heart, kidney, liver, pancreas, pituitary, spleen, skeletal muscle, adrenal gland. Immunogold labeling tissues embedded acrylic resin LR Gold strong mitochondria all However, anterior...
Macrophages are reservoirs for replicating mycobacterium during tuberculosis (TB) infections. In this study, small molecules to be developed as anti-tubercular treatments were investigated their ability kill intracellular bacteria in vitro macrophage models. High-content imaging technologies offer a high-throughput method quantify drug's inhibit Mycobacterium invasion and multiplication host cells. Dedicated image analysis enables the automated quantification of infected macrophages,...
Problem child: The application of signaling DNA-aptamer technology to the development and execution a high-throughput screen for an otherwise problematic target, adenosine deaminase (ADA), is reported. approach employed DNA aptamer that reports on concentration (see scheme). assay was robust in more than 44 000 molecules revealed new competitive inhibitor deaminase.
New antimalarial agents that exhibit multistage activities against drug-resistant strains of malaria parasites represent good starting points for developing next-generation therapies. To facilitate the progression such into development phase, we developed an image-based parasitological screening method defining drug effects on different asexual life cycle stages Plasmodium falciparum. High-throughput a newly assembled diversity-oriented synthetic library using this approach led to...
Mitochondrial aspartate aminotransferase (mAspAT) (E.C. 2.6.1.1), an important enzyme in amino acid metabolism, is identical to a fatty acid-binding protein (FABPpm) isolated from plasma membranes of several cell types. Employing monospecific polyclonal antibody rat mAspAT, we have used immunogold electron microscopy study the subcellular distribution mAspAT various mammalian tissues. Immunogold labeling tissue sections embedded LR Gold resin showed strong mitochondria all tissues examined...
We identified a novel class of aryl-substituted triazine compounds as potent non-nucleoside reverse transcriptase inhibitors (NNRTIs) during high-throughput screening campaign that evaluated more than 200000 for antihuman immunodeficiency virus (HIV) activity using cell-based full replication assay. Herein, we disclose the optimization antiviral in assay system leading to discovery compound 27, which possessed excellent potency against wild-type HIV-1 (EC50 = 0.2 nM) well viruses bearing...
Tuberculosis is a major problem in public health. While new effective treatments to combat the disease are currently under development, they tend suffer from poor solubility often resulting low and/or inconsistent oral bioavailability. Mesoporous materials here investigated an vitro intracellular assay, for delivery of compound PA-824; poorly soluble bactericidal agent being developed against (TB). enhance however, this not translated into higher antibacterial activity TB-infected...
High-throughput screening (HTS) generates an abundance of data that are a valuable resource to be mined. Dockers and miners can use "real-world" HTS test further develop their tools. A screen 50,000 diverse small molecules was carried out against Escherichia coli dihydrofolate reductase (DHFR) compared with previous compounds the same target. Identical assays conditions were maintained for both studies. Prior completion second screen, original publicly released as "training set",...
A total of 140,000 compounds were screened in a targetfree cell-based high throughput assay against HIV-1 infection, and subset 81 promising was identified. Secondary screening these revealed two putative human RNaseH2 inhibitors, RHI001 RHI002, with IC50 value 6.8 μM 16 μM, respectively. RHI002 showed selective activity while inhibited HIV-RNaseH, E. coli RNaseH, RNaseH1 28.5 7.9 31.7 Kinetic analysis that both inhibitors had non-competitive inhibitor-like properties. Because is involved...