Homo and Heterodimer Ligands: the Twin Drug Approach

Publisher Summary Drugs containing two pharmacophoric groups covalently bounded are called twin drugs. This chapter focuses on the combination of only two (identical or nonidentical) pharmacological entities. The association of two identical pharmacophoric entities will generate an “identical twin drug” which is equivalent to a homodimer derivative. The first design strategy is equivalent to a duplication/dimerization process of an active compound or lead. The aim of this approach is the production of a more potent and/or more selective drug compared to the single entity. The administration of twin drugs can be favorable compared to the two separated drugs. The new entity has its own pharmacokinetic property (absorption, distribution, and metabolism) and pharmacodynamic property. These properties will be more predictable compared to the administration of two separated drugs. The duplication of the pharmacophore leads to an equivalent or more active derivative, which exhibits a different selectivity profile and pharmacokinetic properties. Identical twin drugs have shown increasing potencies and/or modified selectivity profiles as receptor ligands when compared to their corresponding single drug. Medicinal chemists should take into account the use of the twin drug approach as soon as they get a lead compound that needs to be optimized.