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Lead Identification

Lead Identification for students,scholars,researchers...

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Lead Identification

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  1. Lead Identification

  2. After screening out the compounds showing potential activity against the target through the hit identification stage, it is necessary to carry out further characterization and optimization of these hit compounds. And this stage is termed as hit to lead. The goal of this stage is to identify the most promising hit series through limited structure-activity relationship (SAR) studies to enter the lead optimization and preclinical development stage. With a dedicated team of skilled scientists and technicians, Creative Biostructure provides MagHelix™ hit evaluation and lead identification (hit to lead) solutions to meet our clients’ needs and goals.

  3. Whether your therapeutic goal focuses on the development of small molecules, peptides, or other biologics, Creative Biostructure can ensure that the performance of your initial hits is significantly improved to meet the standards required to enter the lead optimization stage. We can prioritize and classify the hit compounds identified through screening platforms and utilize advanced biophysical techniques to analyze the target-ligand binding modes. In addition, computer-aided drug design (CADD) tools can help you perform pharmacophore modeling, QSAR analysis, ADME/T prediction, etc. The molecules after the hit to lead stage are the most likely potential leads, which have enhanced potency, reduced off-target activity, and predicted physiochemical/metabolic properties of reasonable in vivo pharmacokinetics.

  4. Hit Biophysical Characterization

  5. As drug discovery enters the hit to lead stage, more detailed information on hit compounds is needed to guide the choice of the best compounds for the next step. Creative Biostructure provides a variety of mainstream biophysical techniques for the identification and characterization of hit compounds. Information obtained can range from simply determining whether the ligand interacts with the target, to binding specificity and information about the binding mode. For example, biophysical assays detect the binding affinities between a hit and the target by Nuclear Magnetic Resonance (NMR), Isothermal Titration Calorimetry (ITC), Dynamic Light Scattering (DLS), and Surface Plasmon Resonance (SPR) techniques. We can also obtain structural information of target-ligand complexes and characterize the binding sites by assays such as X-ray crystallography, Cryo-electron microscopy (Cryo-EM), and NMR. These data are the basis for lead compound discovery and optimization.

  6. References • Fuller N.; et al. An improved model for fragment-based lead generation at AstraZeneca. Drug Discovery Today. 2016, 21(8): 1272-1283. • Alam S, Khan F. 3D-QSAR studies on Maslinic acid analogs for anticancer activity against breast cancer cell line MCF-7. Scientific Reports. 2017, 7(1): 1-13. • Hoffer L.; et al. Chemistry-driven hit-to-lead optimization guided by structure-based approaches. Molecular Informatics. 2018, 37(9-10): 1800059. • Neves B J.; et al. QSAR-based virtual screening: advances and applications in drug discovery. Frontiers in Pharmacology. 2018, 9: 1275.

  7. Excerpt from: https://drug-discovery.creative-biostructure.com/hit-to-lead-p44

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