A chemical biology view of bioactive small molecules and a binder-based approach to connect biology to precision medicines

Introduction Introduction Conclusion References A simplistic view of drug discovery is that it begins, most often using \"model organisms\", with biological inferences of a disease that suggest the need to interfere with some activity, function or process. An enzyme should be inhibited or a pathogen should be killed. Chemical experimentation yields the desired inhibitor, and clinical investigations then test the underlying hypothesis in humans. If the stars align, an effective drug emerges.\n\nThe high cost of testing and low rate of success of this paradigm has led the drug-discovery enterprise to search for new and more effective approaches. In this essay, I explore a concept that focuses on the discovery of compounds that bind targets rather than inhibit a biochemical activity. I present evidence that such binders can affect protein activity in under-app ...