Druglikeness is a qualitative concept used in drug design for how "druglike" a substance is. It is estimated from the molecular structure before the substance is even synthesized and tested. Druglikeness can be estimated for any molecule, and does not evaluate the actual specific effect that the drug achieves (biological activity). A druglike molecule has properties like this:

• Optimal solubility to both water and fat, because an orally administered drug has to go through the intestinal lining, carried in aqueous blood and penetrate the lipid cellular membrane to reach the inside of a cell. The model compound for the cellular membrane is octanol, so the logarithm of the octanol/water partition coefficient, known as ClogP, is used to estimate solubility.
• Since the drug is transported in aqueous media like blood and intracellular fluid, it has to be sufficiently water-soluble. Solubility in water can be estimated from the number of hydrogen bond donors vs. alkyl sidechains in the molecule. Low water solubility translates to slow absorption and action. Too many hydrogen bond donors, on the other hand, lead to low fat solubility, so that the drug cannot penetrate the cell wall to reach the inside of the cell.
• Molecular weight: the smaller, the better, because diffusion is directly affected. 80% of traded drugs have molecular weights under 450 daltons; they belong to the group of small molecules.
• Substructures that have known pharmacological properties.

Also, other factors such as substructures with known toxic, mutagenic or teratogenic properties affect the usefulness of a designed molecule. In fact, several poisons have a good druglikeness. Natural toxins are used in pharmacological research to find out their mechanism of action, and if it could be exploited for beneficial purposes.

One test for druglikeness is Lipinski's Rule of Five.

[edit] External links

• OSIRIS Property Explorer: Prediction of druglikeness

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