CFTR

Target id: 707

Nomenclature: CFTR

Family: CFTR

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for CFTR in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1480 7q31-q32 CFTR cystic fibrosis transmembrane conductance regulator
Mouse - 1476 6 A3 Cftr cystic fibrosis transmembrane conductance regulator
Rat - 1476 4q21 Cftr cystic fibrosis transmembrane conductance regulator
Previous and Unofficial Names
ABCC7
ABC35
CFTR/MRP
MRP7
TNR-CFTR
ATP-binding cassette sub-family C member 7
cAMP-dependent chloride channel
cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7)
Database Links
DrugBank Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
KEGG Gene
OMIM
Orphanet
UniProtKB
Wikipedia
Functional Characteristics
γ = 6-10 pS; permeability sequence = Br- ≥ Cl- > I- > F-, (PI/PCl = 0.1–0.85); slight outward rectification; phosphorylation necessary for activation by ATP binding at binding nucleotide binding domains (NBD)1 and 2; positively regulated by PKC and PKGII (tissue specific); regulated by several interacting proteins including syntaxin 1A, Munc18 and PDZ domain proteins such as NHERF (EBP50) and CAP70

Download all structure-activity data for this target as a CSV file

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Voltage-dependent (mV) Reference
felodipine Hs Potentiation 8.4 pKi - no 1
pKi 8.4 (Ki 4x10-9 M) [1]
Not voltage dependent
capsaicin Hs Potentiation - - - no

Not voltage dependent
nimodipine Hs Potentiation - - - no

Not voltage dependent
genistein Hs Potentiation - - - no

Not voltage dependent
apigenin Hs Potentiation - - - no

Not voltage dependent
CBIQ Hs Potentiation - - - no

Not voltage dependent
NS004 Hs Potentiation - - - no

Not voltage dependent
phenylglycine-01 Hs Potentiation - - - no

Not voltage dependent
sulfonamide-01 Hs Potentiation - - - no

Not voltage dependent
UCCF-029 Hs Potentiation - - - no

Not voltage dependent
UCCF-339 Hs Potentiation - - - no

Not voltage dependent
UCCF-853 Hs Potentiation - - - no

Not voltage dependent
ivacaftor Hs Potentiation - - - no

Not voltage dependent
Activator Comments
UCCF-339, UCCF-029, apigenin and genistein are examples of flavones. UCCF-853 and NS004 are examples of benzimidazolones. CBIQ is an example of a benzoquinoline. felodipine and nimodipine are examples of 1,4-dihydropyridines. Phenylglycine-01 is an example of a phenylglycine. SF-01 is an example of a sulfonamide.
Inhibitors
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Voltage-dependent (mV) Reference
crofelemer Hs Inhibition 5.2 pIC50 - no 3
pIC50 5.2 (IC50 7x10-6 M) [3]
Not voltage dependent
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Voltage-dependent (mV) Reference
glibenclamide Hs - 4.7 pKi - no 2
pKi 4.7 (Ki 2.18x10-5 M) [2]
Not voltage dependent
intracellular CFTRinh-172 Hs - - - - no
intracellular application prolongs mean closed time
Not voltage dependent
GaTx1 Hs - - - - no

Not voltage dependent
extracellular GlyH-101 Hs - - - - no

Not voltage dependent
Channel Blocker Comments
Malonic acid hydrazide conjugates are also CFTR channel blockers (see Verkman and Galietta, 2009 [4]).
Clinically-Relevant Mutations and Pathophysiology
Disease:  Bronchiectasis with or without elevated sweat chloride 1, BESC1
Synonyms: Bronchiectasis [Disease Ontology: DOID:9563]
Idiopathic bronchiectasis [Orphanet: ORPHA60033]
Disease Ontology: DOID:9563
OMIM: 211400
Orphanet: ORPHA60033
Disease:  Congenital bilateral absence of vas deferens
OMIM: 277180
Orphanet: ORPHA48
Disease:  Cystic fibrosis
Disease Ontology: DOID:1485
OMIM: 219700
Orphanet: ORPHA586
Disease:  Hereditary pancreatitis
Synonyms: Hereditary chronic pancreatitis [Orphanet: ORPHA676]
OMIM: 167800
Orphanet: ORPHA676
Disease:  Male infertility with normal virilization due to meiosis defect
Orphanet: ORPHA217034

References

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1. Pedemonte N, Boido D, Moran O, Giampieri M, Mazzei M, Ravazzolo R, Galietta LJ. (2007) Structure-activity relationship of 1,4-dihydropyridines as potentiators of the cystic fibrosis transmembrane conductance regulator chloride channel. Mol. Pharmacol.72 (1): 197-207. [PMID:17452495]

2. Sheppard DN, Welsh MJ. (1992) Effect of ATP-sensitive K+ channel regulators on cystic fibrosis transmembrane conductance regulator chloride currents. J. Gen. Physiol.100 (4): 573-91. [PMID:1281220]

3. Tradtrantip L, Namkung W, Verkman AS. (2010) Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels. Mol. Pharmacol.77 (1): 69-78. [PMID:19808995]

4. Verkman AS, Galietta LJ. (2009) Chloride channels as drug targets. Nat Rev Drug Discov8 (2): 153-71. [PMID:19153558]

How to cite this page

CFTR: CFTR. Last modified on 26/01/2015. Accessed on 25/06/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=707.