Drug discovery is built on a seductive simplification: identify the malfunctioning receptor, design a compound that engages it, and restore function. But many diseases don't cooperate with that assumption. Alzheimer's, metabolic disease, psychiatric pharmacology — each carries evidence of multi-receptor architecture. Multi-target GPCR pharmacology is not a workaround. In certain disease architectures, it is the pharmacologically correct approach.

GPCR biologic drugs stabilize receptor active states through distributed contact networks small molecules have trouble reproducing. The affinity-trap account, treated as a model rather than a verdict, explains a recurring difficulty at family B GPCR programs.