Publication date: Feb 05, 2019
Medicinal chemists are accountable for embedding the appropriate drug target profile into the molecular architecture of a clinical candidate. An accurate characterization of the functional effects following binding of a drug to its biological target is a fundamental step in the discovery of new medicines, informing the translation of preclinical efficacy and safety observations into human trials. Membrane-bound proteins, particularly ion channels and G protein-coupled receptors (GPCRs), are biological targets prone to allosteric modulation. Investigations using allosteric drug candidates and chemical tools suggest that their functional effects may be tailored with a high degree of translational alignment, making them molecular tools to correct pathophysiological functional tone and enable personalized medicine, when a causative target-to-disease link is known. We present select examples of functional molecular fine-tuning of allosterism and discuss consequences relevant to drug design.
Coughlin, Q., Hopper, A.T., Blanco, M.J., , Tirunagaru, Robichaud, A.J., and Doller, D. Allosteric Modalities for Membrane-Bound Receptors: Insights from Drug Hunting for Brain Diseases. 04040. 2019 J Med Chem.
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