Lead Compound Optimization Service

A lead compound is a compound with pharmacological or biological activity that can be used to develop new drugs. Its chemical structure can be further modified to improve potency, selectivity and pharmacokinetic properties. This process is called lead compound optimization.

Once lead compounds are successfully identified, those safe and effective drug candidates are introduced into the preclinical experimental stage through lead compound optimization. Relevant properties of lead compounds are usually improved in multiple DMTA cycles (design-make-test-analyze), such as affinity, selectivity, mode of action, synthesizeability, and ADMET properties.

Lead compound optimization is a key step in the development of new drugs, which can improve the pharmacokinetic properties of lead compounds, prolong the action time of drugs in vivo, enhance metabolic stability and improve bioavailability.

STEMart has launched a series of advanced technologies to facilitate various analyzes in the optimization process of lead compounds, so as to provide rich data information and promote users to make the most reasonable decisions in the optimization process of lead compounds.

Optimization Purpose

The structure of the lead compound is modified to reduce the defects of the lead compound, such as insufficient activity, unstable chemical structure, high toxicity, poor selectivity and unreasonable pharmacokinetic properties.

Service Items

• Develop compounds and their analogues that are easy to synthesize
  • New technologies such as microbatch synthesis can not only be widely used in the field of chemistry using combinatorial synthesis, but can also meet the demand for rapid analysis of millions of compounds under low sample volume conditions (a few nanoliters).
• Establishment of structure-activity relationship of lead compounds
  • Small-angle X-ray scattering and single-crystal X-ray diffraction can provide structural information about protein-ligand complexes to further understand the spatial orientation of ligands. This is crucial for the rational design of selective or effective ligands.
  • Nuclear magnetic resonance (NMR) is a perfect complementary technique for smaller proteins, providing structural information about binding and dynamics under physiological conditions.
• Stability optimization
  • Modern lead optimization tends to understand the details of the temporal stability of protein-analyte complexes as early as possible. This information can be obtained from kinetic constants such as dissociation constants. Surface plasmon resonance (SPR) technology is well suited for this stage because real-time, label-free analysis of kinetics allows direct observation of affinity, IC50, and many other properties.
  • In addition, SPR can provide enthalpy and entropy information, both of which are key features in the lead optimization process. SPR can also be used to further analyze cofactors and media conditions.
• Proteomic optimization
  • Mass spectrometry provides extremely reliable, sensitive, and fast proteomic information. The method also provides information on affinity, selectivity, and binding patterns, as well as other stoichiometric information.
• Toxicological optimization
  • SC-XRD, NMR, SPR and MS techniques are suitable for all types of testing: from determining plasma protein binding and analyzing metabolites to studying distribution and toxicology.

For more information about our lead compound optimization services, please contact us.