Drug-Likeness Assessment

Drug-likeness concepts are helpful for optimization and pharmacokinetic research during drug development. At present, there are molecular description methods such as "Rule-of-Five" to predict and classify the characteristics of drug solubility, chemical stability, and bioavailability. Creative Biolabs analyzes chemical data with high-quality cheminformatics tools to investigate the complex structural information of compounds. We can help customers evaluate drug-likeness and improve existing drug development process.

Introduction of Drug-Likeness

The drug ability of a protein means that a protein can bind a high-affinity ligand with similar drug properties and its activity is regulated by such a ligand. With the deepening of related research, this concept has also been extended to other molecules such as DNA and RNA that can serve as drug targets. For cheminformatics, evaluating "drug-likeness" is an important application that can help medicinal chemists process hits and lead compounds and screen drug candidates that can modulate targets.

In current drug development work, the best strategy is to constantly discover new chemical entities and find candidate drugs that are very similar to existing drugs in terms of key physicochemical and biological properties. Assessment of "drug-likeness" properties helps to obtain more accurate pharmacokinetic and pharmacodynamic data. The main challenge of this work is the dynamic nature and adaptive range of molecular entities, which will greatly affect the prediction results, indicating that we still need to do more research on the structure and physicochemical characterization of bioactive compounds.

Fig.1 The direction of modern drug development. (McCoy, 2014)

Drug-Likeness Assessment

Creative Biolabs evaluates the drug-likeness of compounds through analysis of biologically relevant parameters. The most important part is to distinguish between pharmacodynamic events and pharmacokinetic events, which are the two basic modes of interaction between xenobiotics and biological systems. For biologically active compounds, the interacting biological system consists of pharmacodynamic targets (receptors, ion channels, etc.) and pharmacokinetic factors (exogenous metabolic enzymes, transporters, etc.). The former is characterized by high ligand specificity, especially agonists. In contrast, pharmacokinetic drugs often evolve to low ligand specificity (high confusion) because their role is to recognize and exclude or inactivate a wide variety of substrates.

Our Drug-Likeness evaluation work mainly includes 2 aspects:

• Physical and chemical properties of the drug, such as compound size, shape, lipophilicity, and van der Waals' forces.
• Recognition by proteins that have evolved to be ‘‘promiscuous’’, for example, drug-metabolising enzymes, xenobiotic transporters and serum proteins. Here, molecular properties, such as hydrophobicity and hydrogen bonding ability, play a major role along with some vague pharmacophores, which are defined by the presence of a small number of recognition groups and the variable distance between them.

In addition, in drug development work, the nature of similar drugs should be considered as early as possible in computer design and combinatorial library design. This "drug-likeness" property, that is, the structural and physicochemical properties, supplements a pharmacophore without affecting the pharmacophore while giving the new compound sufficient pharmacokinetic behavior potential.

If you are interested in our drug evaluation services, you can contact us for more details.

Reference

1. Vistoli, G.; et al. Assessing drug-likeness-what are we missing?[J]. Drug discovery today. 2008, 13(7-8): 285-294.

For Research Use Only.