druglike

Druglike is a term used in medicinal chemistry to describe chemical compounds whose structural and physicochemical properties resemble those of established small-molecule therapeutics and are thought to promote favorable pharmacokinetic and safety profiles. It is typically used as a heuristic rather than a formal classification to guide early drug discovery.

Prominent guidelines associated with druglike properties include Lipinski's Rule of Five: molecular weight under 500 Da, logP not greater than 5, no more than 5 hydrogen bond donors, and no more than 10 hydrogen bond acceptors. Additional filters from Veber, Ghose, and other criteria refine the concept by considering rotatable bonds and polar surface area. In practice, druglike compounds balance potency with oral bioavailability, metabolic stability, and low risk of toxicity.

Applications: In screening libraries and lead optimization, researchers favor structures with druglike properties to increase the probability of developing a viable oral drug. The concept also informs decisions about solubility, permeability, metabolic stability, and synthetic feasibility.

Limitations: Druglikeness is a heuristic, not a guarantee of success. Many approved drugs violate one or more guidelines, and natural products, macrocycles, peptides, and biologics may be valuable despite lacking typical druglike features. The field evolves with new modalities that extend beyond traditional small molecules.

See also: Lipinski's Rule of Five; drug-likeness; lead-like; QED (Quantitative Estimate of Drug-likeness); fragment-based drug discovery.