Low amcd values indicated drug pairs related by a simple and usually feasible chemical transformation, usually a functional group change or addition as those found in matched molecular pairs, illustrated in the FDA set for the hydroxylation of L-tyrosine to L-DOPA (Figure ), and in the EGFR set for a Suzuki coupling resulting in a large activity change (Figure ). In the case of the PMB set, low amcd values indicated pairs related by single amino acid exchange often potentially corresponding to a reaction, for example mutation of a glycine to a phenylalanine residue corresponding formally to an α-alkylation of glycine with benzyl bromide (Figure ).