Tuberculosis (TB), a chronic infectious disease caused by Mycobacterium tuberculosis (M. tuberculosis), is the top cause of death from infectious diseases. TB has always accompanied humanity and remains a threat to humanity worldwide: TB is till one of the top ten causes of death worldwide. Treatment of TB is a long process which can bring many side effects. Therefore, the discovery and development of novel effective drugs targeting novel biochemical pathways and treating drug-resistant forms of tuberculosis is an urgent needed worldwide.
In order to promote high-throughput screening (HTS) in antituberculosis drug discovery studies, BOC Sciences has introduced different strategies to design and synthesize two antituberculosis screening libraries capable of generating more than 7,600 drug-like screening compounds that can aim at key protein targets.
Figure 1. Purification and characterization of dUTPase. (Yu, Z.; et al. 2021)
Library Design
2D Similarity-based antituberculosis focused library
The library is developed with 2D fingerprint similarity searches against a reference set of over 20,000 biologically active compounds that are carefully selected from multiple commercial databases. BOC Sciences mainly applies the following therapeutically relevant viral assay data, including Mycobacterium tuberculosis bacterium and related protein targets, protein families:
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Docking-based antituberculosis library
At BOC Sciences, we design this library using a receptor-based approach to provide potential inhibitors of the InhA enzyme, Mycobacterium tuberculosis-specific proteins.
- Firstly, we perform a comprehensive analysis of the crystal structure to investigate the structure of InhA proteins and the binding modes of their known inhibitors
- The BOC Sciences collection of HTS compounds is then processed according to ADME requirements, and all unwanted chemical groups can be filtered out
- The obtained drug-like compound set is screened for the most favorable ligand binding and crystal structure using molecular docking
- Finally, a set of about 3,400 potential anti-TB drugs capable of binding to the InhA protein is obtained based on the docking results
Figure2. Molecular docking of Mt-dUTPase and F0414. (Yu, Z.; et al. 2021)
Antituberculosis Screening Compound Library Characteristics
- No PAINS or toxic substances/unwanted functions: filtered by strict ‘Ro5-like’ physicochemical and most stringent in-house structural filters
- Confirmed bioactivity and safety via preclinical studies and clinical trials
- All of the compounds have been selected by ligand efficacy and predicted binding mode
- Structural diversity, significant efficacy, and cellular penetration
- Structural document, IC50, and other chemical and biological data are provided
- Tanimoto index ≥ 0.80
- All compounds are continually updated
- Compound cherry-picking service is provided
What We Deliver
- Delivered within 2 weeks in any customer-preferred format
- Powders, dry films or DMSO solutions formatted in vials, 96 or 384-well plates
- All compounds have a minimum purity of 90% assessed by 1H NMR and HPLC
- Analytical data is provided
BOC Sciences provides professional, rapid and high-quality services of Antituberculosis Screening Compound Library design at competitive prices for global customers. Personalized and customized services of Antituberculosis Screening Compound Library design can satisfy any innovative scientific study demands. Our clients have direct access to our staff and prompt feedback to their inquiries. If you are interested in our services, please contact us immediately!
Reference
- Yu, Z.; et al. Screening and Identification of a Novel Anti-tuberculosis Compound That Targets Deoxyuridine 5′-Triphosphate Nucleotidohydrolase. Frontiers in Microbiology. 2021. 12: 757914.
