Target Information

Target General Infomation
Target ID
T82028
Former ID
TTDR00347
Target Name
Sodium/hydrogen exchanger 1
Gene Name
SLC9A1
Synonyms
APNH; Myocardial Na+/H+ exchanger; NHE-1; Na(+)/H(+) exchanger 1; Na(+)Sodium/hydrogen exchanger 1/H(+) exchanger 1; Na+/H+ antiporter, amiloride-sensitive; SLC9A1
Target Type
Clinical Trial
Disease Angina pectoris [ICD9: 413; ICD10: I20]
Cardiac arrhythmias [ICD9: 427; ICD10: I47-I49]
Heart arrhythmia [ICD10: I47-I49]
Myocardial infarction [ICD9: 410; ICD10: I21, I22]
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
T82028
UniProt ID
P19634
Sequence
MVLRSGICGLSPHRIFPSLLVVVALVGLLPVLRSHGLQLSPTASTIRSSEPPRERSIGDV
TTAPPEVTPESRPVNHSVTDHGMKPRKAFPVLGIDYTHVRTPFEISLWILLACLMKIGFH
VIPTISSIVPESCLLIVVGLLVGGLIKGVGETPPFLQSDVFFLFLLPPIILDAGYFLPLR
QFTENLGTILIFAVVGTLWNAFFLGGLMYAVCLVGGEQINNIGLLDNLLFGSIISAVDPV
AVLAVFEEIHINELLHILVFGESLLNDAVTVVLYHLFEEFANYEHVGIVDIFLGFLSFFV
VALGGVLVGVVYGVIAAFTSRFTSHIRVIEPLFVFLYSYMAYLSAELFHLSGIMALIASG
VVMRPYVEANISHKSHTTIKYFLKMWSSVSETLIFIFLGVSTVAGSHHWNWTFVISTLLF
CLIARVLGVLGLTWFINKFRIVKLTPKDQFIIAYGGLRGAIAFSLGYLLDKKHFPMCDLF
LTAIITVIFFTVFVQGMTIRPLVDLLAVKKKQETKRSINEEIHTQFLDHLLTGIEDICGH
YGHHHWKDKLNRFNKKYVKKCLIAGERSKEPQLIAFYHKMEMKQAIELVESGGMGKIPSA
VSTVSMQNIHPKSLPSERILPALSKDKEEEIRKILRNNLQKTRQRLRSYNRHTLVADPYE
EAWNQMLLRRQKARQLEQKINNYLTVPAHKLDSPTMSRARIGSDPLAYEPKEDLPVITID
PASPQSPESVDLVNEELKGKVLGLSRDPAKVAEEDEDDDGGIMMRSKETSSPGTDDVFTP
APSDSPSSQRIQRCLSDPGPHPEPGEGEPFFPKGQ
Drugs and Mode of Action
Drug(s) Zoniporide hydrochloride Drug Info Phase 3 Angina pectoris [526547]
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 5'-(N-ethyl-N-isopropyl)amiloride Drug Info [528830]
BIIB-513 Drug Info [543981]
CARIPORIDE Drug Info [530180]
ENIPORIDE Drug Info [534705]
HOE-694 Drug Info [534413]
Homoserine Lactone Drug Info [551393]
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-m-Tolyl-furan-2-carbonyl)-guanidine Drug Info [527509]
N-(5-Methanesulfonyl-2-methyl-benzoyl)-guanidine Drug Info [534413]
N-(5-o-Tolyl-furan-2-carbonyl)-guanidine Drug Info [527509]
N-(5-Phenyl-furan-2-carbonyl)-guanidine Drug Info [527509]
N-[2-(1H-benzoimidazol-2-yl)-benzoyl]-guanidine Drug Info [528720]
N-[4-(1H-benzoimidazol-2-yl)-benzoyl]-guanidine Drug Info [528720]
N-[5-(2-Ethyl-phenyl)-furan-2-carbonyl]-guanidine Drug Info [527509]
N-[5-(2-Nitro-phenyl)-furan-2-carbonyl]-guanidine Drug Info [527509]
Zoniporide hydrochloride Drug Info [526547], [531635]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
DRM DRM Info
Pathways
KEGG Pathway cAMP signaling pathway
Cardiac muscle contraction
Adrenergic signaling in cardiomyocytes
Regulation of actin cytoskeleton
Thyroid hormone signaling pathway
Salivary secretion
Gastric acid secretion
Pancreatic secretion
Bile secretion
Proteoglycans in cancer
Pathway Interaction Database Endothelins
RhoA signaling pathway
ErbB1 downstream signaling
Signaling mediated by p38-alpha and p38-beta
Reactome Hyaluronan uptake and degradation
WikiPathways Regulation of Actin Cytoskeleton
G Protein Signaling Pathways
Glycosaminoglycan metabolism
Osteoclast Signaling
References
Ref 526547Zoniporde: a potent and selective inhibitor of the human sodium-hydrogen exchanger isoform 1 (NHE-1). Cardiovasc Drug Rev. 2003 Spring;21(1):17-32.
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 526547Zoniporde: a potent and selective inhibitor of the human sodium-hydrogen exchanger isoform 1 (NHE-1). Cardiovasc Drug Rev. 2003 Spring;21(1):17-32.
Ref 527509J Med Chem. 2005 Apr 21;48(8):2882-91.(5-Arylfuran-2-ylcarbonyl)guanidines as cardioprotectives through the inhibition of Na+/H+ exchanger isoform-1.
Ref 528720Bioorg Med Chem Lett. 2007 May 1;17(9):2430-3. Epub 2007 Feb 17.Benzimidazol-2-yl or benzimidazol-2-ylthiomethyl benzoylguanidines as novel Na+/H+ exchanger inhibitors, synthesis and protection against ischemic-reperfusion injury.
Ref 528830J Biol Chem. 2007 Jul 6;282(27):19716-27. Epub 2007 May 10.NHE1 inhibition by amiloride- and benzoylguanidine-type compounds. Inhibitor binding loci deduced from chimeras of NHE1 homologues with endogenous differences in inhibitor sensitivity.
Ref 530180Eur J Med Chem. 2009 Sep;44(9):3771-6. Epub 2009 May 5.Synthesis and bioactivity of substituted indan-1-ylideneaminoguanidine derivatives.
Ref 531635Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36.
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 543981(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 948).
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.