Drug likeness: what do bioavailability and toxicity properties tell us about druglikeness?

Druglikeness is a qualitative concept used in drug design for an estimate on how "druglike" a prospective compound is. Usually it is estimated from the molecular structure, often even before the substance is synthesized and tested.

A good drug should show good availability, low toxicity and high potency. The quantitative measures of such properties are bioavailability (BA, measured in %), Maximum Recomended Daily Dose (MRDD, mmol/L) and IC50 against a drug's target.

The product of toxicity and availability, MRDD*BA, gives an upper bound on target IC50 and hence is an indication of a drug quality. The Figure above represents the distribution of such product for slightly over 100 drugs. As it can be seen from the Graph, most of drug compounds have the product small, roughly below 2*10^-5mol/L. Hence, small value of MRDD*BA product may be regarded as an indication of druglikeness.

In fact the situation gets even more interesting if the same druglikeness parameter is plotted in log-scale (see the Figure on the right). Since MRDD*BA limits drug's IC50 against its target, we can deduce that most drugs are centered around pIC50 = 5 (which means that the target pIC50 should exceed 5).