Designed multiple ligands in metabolic disease research: from concept to platform

Type 2 diabetes mellitus (T2DM) is a multifactorial disease, and drug monotherapy typically results in unsatisfactory treatment outcomes for patients. Even when used in combination, existing therapies lack efficacy in the long term. Designed multiple ligands (DMLs) are compounds developed to modulate multiple targets relevant to a disease. DMLs offer the potential to yield greater efficacy over monotherapies, either by modulating different biological pathways, or by boosting a single one. However, examples of DMLs progressing into clinical trials, or onto the market are rare; DML drug discovery is challenging, and perceived by some to be almost impossible. Nevertheless, with the judicious selection of biological targets, both from a biological and chemical perspective, it is possible to develop drug-like DMLs.

► Designed multiple ligands (DMLs) modulate multiple targets relevant to a disease.
► DMLs give enhanced efficacy by modulating multiple biological pathways or by boosting a single one.
► The development of DMLs is challenging and few have reached clinical trials or the market.
► A drug-discovery platform for the development of DMLs for type 2 diabetes mellitus has been created.