Lead Optimization Service

Lead optimization marks the end of the drug discovery and development process, in which the task is to advance the drug toward safety and efficacy, and ensure that it ultimately enters the market. Our company provides you with professional strategies to accelerate the assessment for your small molecule candidates enable your selection of lead candidate to quickly and efficiently enter the development in autoimmune diseases and inflammation.

Lead Optimization

As one the of most stubborn bottlenecks in the drug discovery process, lead optimization may undergo Iterative cycles of amelioration to balance the potency, selectivity, toxicity, synthesisability and other pharmacological properties of the hit candidate compounds. During the design, make, test, analyse (DMTA) cycle, candidate drugs are designed in silico and then made to try out the hypotheses through experiments and examination, and subsequently relevant pharmacokinetic data are obtained and analyzed for new discoveries and knowledge.

Iterative lead optimization cycleFig.1 Iterative lead optimization cycle (Heifetz A., et al., 2018)

  • Design
    Computer-aided drug design against a particular site for a target comprised of extensive used structure-based design (SBDD) and ligand-based design (LDBB). The SBDD method based on the three-dimensional structure analyzes the important biological functional sites of the molecular target and analyzes its interaction with other substances. While the LBDD takes the known drug ligand as the target, analyzes the activity relationship between the target and the drug from the perspective of structure-activity relationship (SAR), providing guidance for optimizing various properties of the drug.
  • Make
    Chemical synthesis of candidate drugs needs to be readily achievable. In combination with computer-aided synthesis tools, reaction prediction, automated synthesis, and retrosynthetic analysis have been applied to automated drug synthesis and optimization in short cycles. In the field of synthetic chemistry, modifications such as asymmetric hydrogenation, asymmetric epoxidation, fluorination and trifluoromethylation of C-H bonds have become new directions in medicinal chemistry.
  • Test
    The structure of the target compound needs to be confirmed by spectroscopies, NMR, mass spectrometry, X-ray single crystal diffraction or X-ray powder diffraction and other physical and chemical methods. In parallel, biological assay in cells, organoids and spheroids in vitro models is necessary to be performed to obtain drug properties
  • Analyse
    Data obtained during the testing stage require rigorous, computer-aided in-depth analysis of SAR to accurately assess drug properties and guide optimization, and achieve the purpose of saving optimization cycle time and labor as much as possible.

Our Services

Lead optimization aims at enhancing the market potential of candidate compounds. Our company provides you with professional and meticulous lead optimization services for drug development related to autoimmune diseases & inflammation. Our services include but not limited to:

Binding Mode Identification

  • X-ray crystallography
  • NMR spectroscopy
  • Electron microscopy

Computer-Aided Drug Design

  • Structure-based molecular modeling
  • Ligand-based molecular modeling
  • Fragment-based ligand Design
  • 3D databases

In silico Prediction

  • Physiochemical properties
  • SAR/QSAR prediction
  • Comparative molecular surface/field analysis
  • Structure neighborhoods identification

Optimization

  • Surface plasmon resonance (SPR) analysis
  • Constrained or multi-objective optimization by atom addition, bond addition or bond removal
  • Free-energy perturbation guided optimization

As one of the most mature practical services, the SPR analysis we provide aim at addressing affinity analysis, kinetic analysis, molecule-protein interaction and molecule- nucleic acid interaction, etc.

Lead Optimization Service

Our Advantages

Specific services on a case-by-case basis

Specific services on a case-by-case basis

Experienced and multidisciplinary team

Experienced and multidisciplinary team

Rigorous experimental guidelines and standards

Rigorous experimental guidelines and standards

Well-equipped and first-class laboratories

Well-equipped and first-class laboratories

With the participation of professionals from multiple disciplines, our company will help you make comprehensive measurement for the characteristics of your small molecule candidates and optimize them on a multidimensional specifically to ensure that they can reach the market standards as soon as possible. If you are interested in our services, please contact us for more detailed information.

Reference

  1. Heifetz, Alexander et al. "Computational Methods Used in Hit-to-Lead and Lead Optimization Stages of Structure-Based Drug Discovery." Methods in molecular biology 1705 (2018): 375-394.
For research use only. Not intended for any clinical use.