Target Information

Target General Infomation
Target ID
T92403
Former ID
TTDR00035
Target Name
Sodium/hydrogen exchanger 3
Gene Name
SLC9A3
Synonyms
NHE-3; Na(+)/H(+) exchanger 3; SLC9A3
Target Type
Clinical Trial
Disease Angina pectoris [ICD9: 413; ICD10: I20]
Chronic kidney disease [ICD9: 403, 585.1-585.5, 585.9; ICD10: N18]
Cheyne-stokes respiration [ICD10: R06.3]
Cardiac arrhythmias [ICD9: 427; ICD10: I47-I49]
Constipation [ICD9: 564; ICD10: K59.0]
Heart arrhythmia [ICD10: I47-I49]
Renal disease [ICD10: N00-N29]
Function
Involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient. Plays an important role in signal transduction.
BioChemical Class
Monovalent cation:proton antiporter
Target Validation
T92403
UniProt ID
P48764
Sequence
MWGLGARGPDRGLLLALALGGLARAGGVEVEPGGAHGESGGFQVVTFEWAHVQDPYVIAL
WILVASLAKIGFHLSHKVTSVVPESALLIVLGLVLGGIVWAADHIASFTLTPTVFFFYLL
PPIVLDAGYFMPNRLFFGNLGTILLYAVVGTVWNAATTGLSLYGVFLSGLMGDLQIGLLD
FLLFGSLMAAVDPVAVLAVFEEVHVNEVLFIIVFGESLLNDAVTVVLYNVFESFVALGGD
NVTGVDCVKGIVSFFVVSLGGTLVGVVFAFLLSLVTRFTKHVRIIEPGFVFIISYLSYLT
SEMLSLSAILAITFCGICCQKYVKANISEQSATTVRYTMKMLASSAETIIFMFLGISAVN
PFIWTWNTAFVLLTLVFISVYRAIGVVLQTWLLNRYRMVQLEPIDQVVLSYGGLRGAVAF
ALVVLLDGDKVKEKNLFVSTTIIVVFFTVIFQGLTIKPLVQWLKVKRSEHREPRLNEKLH
GRAFDHILSAIEDISGQIGHNYLRDKWSHFDRKFLSRVLMRRSAQKSRDRILNVFHELNL
KDAISYVAEGERRGSLAFIRSPSTDNVVNVDFTPRSSTVEASVSYLLRENVSAVCLDMQS
LEQRRRSIRDAEDMVTHHTLQQYLYKPRQEYKHLYSRHELTPTEDEKQDREIFHRTMRKR
LESFKSTKLGLNQNKKAAKLYKRERAQKRRNSSIPNGKLPMESPAQNFTIKEKDLELSDT
EEPPNYDEEMSGGIEFLASVTKDTASDSPAGIDNPVFSPDEALDRSLLARLPPWLSPGET
VVPSQRARTQIPYSPGTFCRLMPFRLSSKSVDSFLQADGPEERPPAALPESTHM
Drugs and Mode of Action
Drug(s) AVE-0657 Drug Info Phase 2 Cheyne-stokes respiration [522222]
AZD1722 Drug Info Phase 2 Renal disease [524182]
AZD1772//RDX5791 Drug Info Phase 2 Chronic kidney disease [550265]
RDX-5791 Drug Info Phase 2 Constipation [523444]
CARIPORIDE Drug Info Discontinued in Phase 2 Angina pectoris [545749]
ENIPORIDE Drug Info Discontinued in Phase 2 Cardiac arrhythmias [546734]
HOE-694 Drug Info Terminated Heart arrhythmia [534245]
Inhibitor AVE-0657 Drug Info [532610]
CARIPORIDE Drug Info [534705]
ENIPORIDE Drug Info [534705]
HOE-694 Drug Info [534413]
N-(3-Methanesulfonyl-4-methoxy-benzoyl)-guanidine Drug Info [534413]
N-(3-Methanesulfonyl-4-methyl-benzoyl)-guanidine Drug Info [534413]
N-(4-Bromo-3-methanesulfonyl-benzoyl)-guanidine Drug Info [534413]
N-(4-Chloro-3-methanesulfonyl-benzoyl)-guanidine Drug Info [534413]
N-(4-Cyano-3-methanesulfonyl-benzoyl)-guanidine Drug Info [534413]
N-(5-Methanesulfonyl-2-methyl-benzoyl)-guanidine Drug Info [534413]
Modulator AZD1722 Drug Info [550792]
AZD1772//RDX5791 Drug Info [550792]
RDX-5791 Drug Info [550792]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Proximal tubule bicarbonate reclamation
Protein digestion and absorption
Bile secretion
Mineral absorption
Pathway Interaction Database Endothelins
RhoA signaling pathway
WikiPathways SIDS Susceptibility Pathways
References
Ref 522222ClinicalTrials.gov (NCT00614250) Evaluation of the Effect of AVE0657 on Obstructive Sleep Apnea. U.S. National Institutes of Health.
Ref 523444ClinicalTrials.gov (NCT01340053) A Study to Evaluate the Safety and Efficacy of RDX5791 for the Treatment of Constipation Predominant Irritable Bowel Syndrome (IBS-C). U.S. National Institutes of Health.
Ref 524182ClinicalTrials.gov (NCT01764854) Pharmacodynamic Study of AZD1722 in End-stage Renal Disease Patients on Hemodialysis. U.S. National Institutes of Health.
Ref 534245Effect of Hoe 694, a novel Na(+)-H+ exchange inhibitor, on intracellular pH regulation in the guinea-pig ventricular myocyte. Br J Pharmacol. 1996 Aug;118(8):1905-12.
Ref 545749Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004531)
Ref 546734Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010029)
Ref 550265Clinical pipeline report, company report or official report of Ardelyx.
Ref 532610Inhibition of central Na(+)/H(+) exchanger type 3 can alleviate sleep apnea in Sprague-Dawley rats. Chin Med J (Engl). 2014;127(1):48-53.
Ref 534413J Med Chem. 1997 Jun 20;40(13):2017-34.(2-Methyl-5-(methylsulfonyl)benzoyl)guanidine Na+/H+ antiporter inhibitors.
Ref 534705J Med Chem. 1998 Sep 10;41(19):3736-47.Bicyclic acylguanidine Na+/H+ antiporter inhibitors.
Ref 550792RDX5791, a First-in-Class Minimally Systemic NHE3 Inhibitor in Clinical Development for CIC and IBS-C, Increases Intestinal Sodium Leading to Enhanced Intestinal Fluid Volume and Transit. Gastroenterology. 2011;140(suppl 1):S99.

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