Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6B22QH)

• DOT Name: Cystic fibrosis transmembrane conductance regulator (CFTR)
• Synonyms: CFTR; ATP-binding cassette sub-family C member 7; Channel conductance-controlling ATPase; EC 5.6.1.6; cAMP-dependent chloride channel
• Gene Name: CFTR
• Related Disease:
  Cystic fibrosis
  Congenital bilateral absence of vas deferens
  Hereditary chronic pancreatitis
• UniProt ID: CFTR_HUMAN
• PDB ID: 1XMI ; 1XMJ ; 2BBO ; 2BBS ; 2BBT ; 2LOB ; 2PZE ; 2PZF ; 2PZG ; 3GD7 ; 3ISW ; 4WZ6 ; 5D2D ; 5D3E ; 5D3F ; 5TF7 ; 5TF8 ; 5TFA ; 5TFB ; 5TFC ; 5TFD ; 5TFF ; 5TFG ; 5TFI ; 5TFJ ; 5TGK ; 5UAK ; 6GJQ ; 6GJS ; 6GJU ; 6GK4 ; 6GKD ; 6HEP ; 6MSM ; 6O1V ; 6O2P ; 6UK1 ; 6WBS ; 6ZE1 ; 7QI1 ; 7SV7 ; 7SVD ; 7SVR ; 8EIG ; 8EIO ; 8EIQ ; 8EJ1 ; 8FZQ
• EC Number: 5.6.1.6
• Pfam ID: PF00664 ; PF00005 ; PF14396
• Sequence:
  MQRSPLEKASVVSKLFFSWTRPILRKGYRQRLELSDIYQIPSVDSADNLSEKLEREWDRE
  LASKKNPKLINALRRCFFWRFMFYGIFLYLGEVTKAVQPLLLGRIIASYDPDNKEERSIA
  IYLGIGLCLLFIVRTLLLHPAIFGLHHIGMQMRIAMFSLIYKKTLKLSSRVLDKISIGQL
  VSLLSNNLNKFDEGLALAHFVWIAPLQVALLMGLIWELLQASAFCGLGFLIVLALFQAGL
  GRMMMKYRDQRAGKISERLVITSEMIENIQSVKAYCWEEAMEKMIENLRQTELKLTRKAA
  YVRYFNSSAFFFSGFFVVFLSVLPYALIKGIILRKIFTTISFCIVLRMAVTRQFPWAVQT
  WYDSLGAINKIQDFLQKQEYKTLEYNLTTTEVVMENVTAFWEEGFGELFEKAKQNNNNRK
  TSNGDDSLFFSNFSLLGTPVLKDINFKIERGQLLAVAGSTGAGKTSLLMVIMGELEPSEG
  KIKHSGRISFCSQFSWIMPGTIKENIIFGVSYDEYRYRSVIKACQLEEDISKFAEKDNIV
  LGEGGITLSGGQRARISLARAVYKDADLYLLDSPFGYLDVLTEKEIFESCVCKLMANKTR
  ILVTSKMEHLKKADKILILHEGSSYFYGTFSELQNLQPDFSSKLMGCDSFDQFSAERRNS
  ILTETLHRFSLEGDAPVSWTETKKQSFKQTGEFGEKRKNSILNPINSIRKFSIVQKTPLQ
  MNGIEEDSDEPLERRLSLVPDSEQGEAILPRISVISTGPTLQARRRQSVLNLMTHSVNQG
  QNIHRKTTASTRKVSLAPQANLTELDIYSRRLSQETGLEISEEINEEDLKECFFDDMESI
  PAVTTWNTYLRYITVHKSLIFVLIWCLVIFLAEVAASLVVLWLLGNTPLQDKGNSTHSRN
  NSYAVIITSTSSYYVFYIYVGVADTLLAMGFFRGLPLVHTLITVSKILHHKMLHSVLQAP
  MSTLNTLKAGGILNRFSKDIAILDDLLPLTIFDFIQLLLIVIGAIAVVAVLQPYIFVATV
  PVIVAFIMLRAYFLQTSQQLKQLESEGRSPIFTHLVTSLKGLWTLRAFGRQPYFETLFHK
  ALNLHTANWFLYLSTLRWFQMRIEMIFVIFFIAVTFISILTTGEGEGRVGIILTLAMNIM
  STLQWAVNSSIDVDSLMRSVSRVFKFIDMPTEGKPTKSTKPYKNGQLSKVMIIENSHVKK
  DDIWPSGGQMTVKDLTAKYTEGGNAILENISFSISPGQRVGLLGRTGSGKSTLLSAFLRL
  LNTEGEIQIDGVSWDSITLQQWRKAFGVIPQKVFIFSGTFRKNLDPYEQWSDQEIWKVAD
  EVGLRSVIEQFPGKLDFVLVDGGCVLSHGHKQLMCLARSVLSKAKILLLDEPSAHLDPVT
  YQIIRRTLKQAFADCTVILCEHRIEAMLECQQFLVIEENKVRQYDSIQKLLNERSLFRQA
  ISPSDRVKLFPHRNSSKCKSKPQIAALKEETEEEVQDTRL
• Function: Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis. Mediates the transport of chloride ions across the cell membrane. Channel activity is coupled to ATP hydrolysis. The ion channel is also permeable to HCO(3)(-); selectivity depends on the extracellular chloride concentration. Exerts its function also by modulating the activity of other ion channels and transporters. Plays an important role in airway fluid homeostasis. Contributes to the regulation of the pH and the ion content of the airway surface fluid layer and thereby plays an important role in defense against pathogens. Modulates the activity of the epithelial sodium channel (ENaC) complex, in part by regulating the cell surface expression of the ENaC complex. Inhibits the activity of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G. Inhibits the activity of the ENaC channel containing subunits SCNN1D, SCNN1B and SCNN1G, but not of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G. May regulate bicarbonate secretion and salvage in epithelial cells by regulating the transporter SLC4A7. Can inhibit the chloride channel activity of ANO1. Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation.
• Tissue Specificity: Expressed in the respiratory airway, including bronchial epithelium, and in the female reproductive tract, including oviduct (at protein level) . Detected in pancreatic intercalated ducts in the exocrine tissue, on epithelial cells in intralobular striated ducts in sublingual salivary glands, on apical membranes of crypt cells throughout the small and large intestine, and on the reabsorptive duct in eccrine sweat glands . Detected on the equatorial segment of the sperm head (at protein level) . Detected in nasal and bronchial superficial epithelium . Expressed by the central cells on the sebaceous glands, dermal adipocytes and, at lower levels, by epithelial cells .
• KEGG Pathway:
  ABC transporters (hsa02010)
  cAMP sig.ling pathway (hsa04024)
  AMPK sig.ling pathway (hsa04152)
  Tight junction (hsa04530)
  Gastric acid secretion (hsa04971)
  Pancreatic secretion (hsa04972)
  Bile secretion (hsa04976)
  Vibrio cholerae infection (hsa05110)
• Reactome Pathway:
  RHO GTPases regulate CFTR trafficking (R-HSA-5627083)
  Defective CFTR causes cystic fibrosis (R-HSA-5678895)
  Ub-specific processing proteases (R-HSA-5689880)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  RHOQ GTPase cycle (R-HSA-9013406)
  Chaperone Mediated Autophagy (R-HSA-9613829)
  Late endosomal microautophagy (R-HSA-9615710)
  Aggrephagy (R-HSA-9646399)
  ABC-family proteins mediated transport (R-HSA-382556)
• BioCyc Pathway: MetaCyc:HS00075-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cystic fibrosis	DIS2OK1Q	Definitive	Autosomal recessive	[1]
Congenital bilateral absence of vas deferens	DISR15UU	Supportive	Autosomal recessive	[2]
Hereditary chronic pancreatitis	DISF0J1Q	Limited	Autosomal dominant	[3]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Chloride	DM1TJXA	Phase 3	Cystic fibrosis transmembrane conductance regulator (CFTR) decreases the secretion of Chloride.	[50]

59 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Cystic fibrosis transmembrane conductance regulator (CFTR).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cystic fibrosis transmembrane conductance regulator (CFTR).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Cystic fibrosis transmembrane conductance regulator (CFTR).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Cystic fibrosis transmembrane conductance regulator (CFTR).	[10]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Cystic fibrosis transmembrane conductance regulator (CFTR).	[7]
Vitamin C	DMXJ7O8	Approved	Vitamin C increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[11]
Sodium phenylbutyrate	DMXLBCQ	Approved	Sodium phenylbutyrate increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[9]
Isoproterenol	DMK7MEY	Approved	Isoproterenol increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[12]
Adenosine	DMM2NSK	Approved	Adenosine increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[12]
Gentamicin	DMKINJO	Approved	Gentamicin increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[13]
Glutathione	DMAHMT9	Approved	Glutathione decreases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[14]
Cilostazol	DMZMSCT	Approved	Cilostazol increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[15]
Glibenclamide	DM8JXPZ	Approved	Glibenclamide decreases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[16]
Niflumic acid	DMJ3I1Q	Approved	Niflumic acid decreases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[17]
Flufenamic Acid	DMC8VNH	Approved	Flufenamic Acid decreases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[18]
Nimodipine	DMQ0RKZ	Approved	Nimodipine increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[19]
Oxidized glutathione	DM9EQC0	Approved	Oxidized glutathione decreases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[14]
Salmeterol	DMIEU69	Approved	Salmeterol increases the expression of Cystic fibrosis transmembrane conductance regulator (CFTR).	[20]
Rhucin	DM3ADGP	Approved	Rhucin increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[15]
Bumetanide	DMRV7H0	Approved	Bumetanide decreases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[21]
Papaverine	DMCA9QP	Approved	Papaverine increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[15]
Milrinone	DM8TUPF	Approved	Milrinone increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[15]
Desmopressin	DMS3GVE	Approved	Desmopressin increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[22]
Ivacaftor	DMZC1HS	Approved	Ivacaftor increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[23]
Miglustat	DM5J64S	Approved	Miglustat increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[24]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[25]
Curcumin	DMQPH29	Phase 3	Curcumin increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[26]
Genistein	DM0JETC	Phase 2/3	Genistein increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[27]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Cystic fibrosis transmembrane conductance regulator (CFTR).	[28]
BAICALEIN	DM4C7E6	Phase 2	BAICALEIN increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[29]
SSR149415	DMCMD93	Phase 2	SSR149415 decreases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[22]
Tetramethylpyrazine	DMC0WNB	Discontinued in Phase 2	Tetramethylpyrazine increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[32]
Trequinsin	DMQRSMD	Terminated	Trequinsin increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[33]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cystic fibrosis transmembrane conductance regulator (CFTR).	[35]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Cystic fibrosis transmembrane conductance regulator (CFTR).	[36]
Forskolin	DM6ITNG	Investigative	Forskolin increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[37]
Okadaic acid	DM47CO1	Investigative	Okadaic acid decreases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[38]
Apigenin	DMI3491	Investigative	Apigenin increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[18]
PD98059	DMZC90M	Investigative	PD98059 decreases the expression of Cystic fibrosis transmembrane conductance regulator (CFTR).	[39]
[3H]cAMP	DMZRQU7	Investigative	[3H]cAMP increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[40]
Serotonin	DMOFCRY	Investigative	Serotonin increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[41]
Nitrosoglutathione	DMZ9WI4	Investigative	Nitrosoglutathione decreases the expression of Cystic fibrosis transmembrane conductance regulator (CFTR).	[42]
H-89	DM4RVGO	Investigative	H-89 decreases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[43]
G418	DMKTJBU	Investigative	G418 increases the expression of Cystic fibrosis transmembrane conductance regulator (CFTR).	[44]
ROLIPRAM	DMJ03UM	Investigative	ROLIPRAM decreases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[45]
isobutylmethylxanthine	DM46F5X	Investigative	isobutylmethylxanthine increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[27]
Chelerythrine	DMCP1G9	Investigative	Chelerythrine decreases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[43]
Bicarbonate	DMT5E36	Investigative	Bicarbonate decreases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[46]
NPPB	DMFIWAN	Investigative	NPPB decreases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[21]
[3H]CGP12177	DMZN1A3	Investigative	[3H]CGP12177 increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[47]
CFTRinh-172	DM8TJW3	Investigative	CFTRinh-172 decreases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[21]
diphenylamine-2-carboxylic acid	DMBV19T	Investigative	diphenylamine-2-carboxylic acid decreases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[16]
Nitrate	DMVFB93	Investigative	Nitrate decreases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[46]
Octanol	DMBGHPE	Investigative	Octanol increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[48]
9-anthroic acid	DMGCVT2	Investigative	9-anthroic acid decreases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[49]
AMP-PNP	DMTOK1D	Investigative	AMP-PNP affects the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[14]
Phorbol 12-myristate	DM096SC	Investigative	Phorbol 12-myristate increases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[40]
Relcovaptan	DM3AWPB	Investigative	Relcovaptan decreases the activity of Cystic fibrosis transmembrane conductance regulator (CFTR).	[22]

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Cystic fibrosis transmembrane conductance regulator (CFTR).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the ubiquitination of Cystic fibrosis transmembrane conductance regulator (CFTR).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cystic fibrosis transmembrane conductance regulator (CFTR).	[31]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Cystic fibrosis transmembrane conductance regulator (CFTR).	[34]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Lumacaftor	DMCLWDJ	Phase 2	Lumacaftor affects the folding of Cystic fibrosis transmembrane conductance regulator (CFTR).	[30]
Kaempferol	DMHEMUB	Investigative	Kaempferol affects the localization of Cystic fibrosis transmembrane conductance regulator (CFTR).	[9]

References

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