How multispecific molecules are transforming pharmacotherapy

Abstract

Over the past several decades, the pharmaceutical industry has progressed from identifying small-molecule natural products with favourable pharmacological properties mediated by unknown molecular mechanisms, to deliberate engineering of chemical compounds and macro-molecules that alter the activities of prespecified targets in predefined ways. The past quarter century has seen the emergence of an entirely new drug category: multispecific molecular drugs that are prospectively designed to engage two or more entities to exert their pharmacological effect. This design elicits emergent properties that endow the drugs with capabilities that are inaccessible to monospecific therapies. Furthermore, these properties enable multispecific drugs to circumvent biological barriers to pharmacology, including rapid clearance, functional redundancy, on-target/off-tissue toxicity, and lack of druggable features. Here, I describe how a new wave of approved multispecific drugs is recalibrating expectations of what can be achieved through pharmacotherapy.