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Chloride transport modulators as drug candidates

Verkman, Alan S ; Galietta, Luis J V

American Journal of Physiology: Cell Physiology, 2021-12, Vol.321 (6), p.C932-C946 [Periódico revisado por pares]

United States: American Physiological Society

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Título:
Chloride transport modulators as drug candidates
Autor: Verkman, Alan S ; Galietta, Luis J V
Assuntos: Acidification ; Animal models ; Animals ; Antiporters - drug effects ; Antiporters - genetics ; Antiporters - metabolism ; Cell membranes ; Cell size ; Chloride ; Chloride channels ; Chloride Channels - drug effects ; Chloride Channels - genetics ; Chloride Channels - metabolism ; Chloride conductance ; Chloride transport ; Chlorides - metabolism ; Constipation ; Cystic fibrosis ; Cystic Fibrosis Transmembrane Conductance Regulator - drug effects ; Cystic Fibrosis Transmembrane Conductance Regulator - genetics ; Cystic Fibrosis Transmembrane Conductance Regulator - metabolism ; Diarrhea ; Drug Design ; Drug development ; Drug Discovery ; Excitability ; Eye disorders ; Genomes ; Goiter ; Hearing loss ; Humans ; Ion Transport ; Ions ; Kidney diseases ; Kidney stones ; Kinetics ; Membrane Transport Modulators - chemistry ; Membrane Transport Modulators - pharmacology ; Muscle contraction ; Mutation ; Myotonia ; Nephrolithiasis ; Nephropathy ; Osteopetrosis ; Osteoporosis ; Polycystic kidney ; Review ; Sulfate Transporters - drug effects ; Sulfate Transporters - genetics ; Sulfate Transporters - metabolism
É parte de: American Journal of Physiology: Cell Physiology, 2021-12, Vol.321 (6), p.C932-C946
Notas: ObjectType-Article-1
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Descrição: Chloride transport across cell membranes is broadly involved in epithelial fluid transport, cell volume and pH regulation, muscle contraction, membrane excitability, and organellar acidification. The human genome encodes at least 53 chloride-transporting proteins with expression in cell plasma or intracellular membranes, which include chloride channels, exchangers, and cotransporters, some having broad anion specificity. Loss-of-function mutations in chloride transporters cause a wide variety of human diseases, including cystic fibrosis, secretory diarrhea, kidney stones, salt-wasting nephropathy, myotonia, osteopetrosis, hearing loss, and goiter. Although impactful advances have been made in the past decade in drug treatment of cystic fibrosis using small molecule modulators of the defective cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, other chloride channels and solute carrier proteins (SLCs) represent relatively underexplored target classes for drug discovery. New opportunities have emerged for the development of chloride transport modulators as potential therapeutics for secretory diarrheas, constipation, dry eye disorders, kidney stones, polycystic kidney disease, hypertension, and osteoporosis. Approaches to chloride transport-targeted drug discovery are reviewed herein, with focus on chloride channel and exchanger classes in which recent preclinical advances have been made in the identification of small molecule modulators and in proof of concept testing in experimental animal models.
Editor: United States: American Physiological Society
Idioma: Inglês

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Chloride transport modulators as drug candidates

Verkman, Alan S ; Galietta, Luis J V

United States: American Physiological Society

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