Allosteric Modalities for Membrane-Bound Receptors: Insights from Drug Hunting for Brain Diseases.
J Med Chem
; 62(13): 5979-6002, 2019 07 11.
Article
in En
| MEDLINE
| ID: mdl-30721063
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neurotransmitter Agents
/
Receptors, G-Protein-Coupled
/
Ion Channels
Limits:
Animals
/
Humans
Language:
En
Journal:
J Med Chem
Journal subject:
QUIMICA
Year:
2019
Type:
Article