druglikeness

Druglikeness is a qualitative measure of how likely a chemical compound is to become an orally active drug, based on its physicochemical properties and structural features. The most widely cited guideline is Lipinski's Rule of Five, a set of criteria linked to oral bioavailability: molecular weight under 500 Da, logP not greater than 5, no more than five hydrogen bond donors, and no more than ten hydrogen bond acceptors. In addition, other heuristics such as Veber's rules (ten or fewer rotatable bonds and polar surface area below about 140 Å^2) further characterize drug-likeness. More modern filters, such as the Egan egg and the Muegge criteria, add nuance by considering additional properties and chemical complexity.

Druglikeness is a guide, not an absolute rule; many approved drugs violate one or more criteria, and conversely, some compounds outside traditional drug-like space can become successful drugs. In practice, drug-likeness informs library design, high-throughput screening prioritization, and early ADMET risk assessment. It is often balanced with the concept of lead-likeness, which favors smaller, less lipophilic molecules that might evolve into drugs with favorable pharmacokinetics.

Ultimately, druglikeness is part of a broader assessment of pharmacokinetics and toxicity (ADMET) that determines a compound’s potential as a therapeutic. Its utility rests on being a useful heuristic—helpful for guiding discovery while recognizing its limitations.