Structure-based drug design is the design and optimization of a hit's structure to make it more suitable for becoming a drug candidate. Based on our knowledge of drug discovery and development, Creative Biolabs provides you structure-based drug design service to meet your needs.

The structure-based design is based on a thoroughly understanding of various characters of a hit (like the mechanism of action, structure-activity relationship), which means how its shape and charge inhibit its targets. Structure-based drug design may lead to identify potential new binding interactions or contribute to improving ADME, potency, and selectivity without disrupting key receptor interactions.

Creative Biolabs provides one-step service for structure-based drug design. Our short outline of this process includes: Primarily, choose a target and evaluate the structure information. Secondary, screening different compound libraries, including target-based libraries, natural compound libraries and FDA approved drug libraries. Thirdly, combined with the advanced structure determination or ligand-protein determination techniques, such as X-ray crystallography or NMR spectroscopy, a series of best binders and their formulation of structure-activity relationships (SAR) are identified. Above steps result in the identification of the active ligand structure that can be optimized to increase potency. After that, several cycles of chemical synthesis, complex structure determination and further optimization is conducted. After several cycles (maybe hundreds of this cycle), optimization in binding, specificity, toxicity, etc. will emerge.

Creative Biolabs has already built several platforms for structure determination.

Inspection

Ligand binding sites are modified and optimized based on interactions of molecules and targets. The newly designed compounds need to be evaluated by scoring algorithms.

Structure-Based Drug Design Figure 1. Inhibitors for thymidylate synthase were designed based on modifications of the cofactor 5,10-methylene tetrahydrofolate. (Anderson 2003)

Virtual Screening

It is a method which searching large scale of 3D structure databases to identify available small molecules and new ligands. Those ligands are scored by fast approximate docking programs. Creative Biolabs offers unparalleled virtual screening service. We are able to predict accurate ligand binding mode and conformation by scoring functions, predicting protein flexibility, detecting and docking binding sites.

De Novo Lead Generation

De novo lead generation can give rise to novel compounds. In this method, small ligand molecules (like benzene rings, carbonyl groups, amino groups, etc.) are built up by assembling small pieces, scored, and linked in silico. Creative Biolabs provides advanced programs to dock and score fragments of compounds according to their primary use. In addition, we can synthesize the intended compounds in the laboratory to confirm their activities.

High Throughput Screening

Apart from computer-based methods mentioned above, Creative Biolabs also provides experimental-based HTS method by combinatorial synthesis, and parallel testing thousands of compounds for biochemical effects. Structures of targets and small compounds are determined by dynamic light scattering (DLS), X-ray crystallography, nuclear magnetic resonance (NMR) spectrometry, cryo-electron microscopy and mass spectrometry (MS).

For more detailed information, please feel free to contact us or directly sent us an inquiry.

Reference

  1. Anderson A C (2003). "The Process of Structure-Based Drug Design" Chemistry & Biology, 10: 787-797. Doi: 10.1016/j.chembiol.2003.09.002

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