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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2008-08-26 17:00:10
Primary Accession Number DB01654
Secondary Accession Number
  • EXPT03311
Name Thiorphan
Drug Type
  • Experimental
  • Small Molecule
Description A potent inhibitor of membrane metalloendopeptidase (enkephalinase). Thiorphan potentiates morphine-induced analgesia and attenuates naloxone-precipitated withdrawal symptoms.
Synonyms Not Available
Brand Names
  1. THIORPHAN
Brand Mixtures Not Available
Chemical IUPAC Name 2-[[2-(phenylmethyl)-3-sulfanylpropanoyl]amino]acetic acid
Chemical Formula C12H15NO3S
Chemical Structure Structure
CAS Registry Number 76721-89-6
InChI Identifier InChI=1/C12H15NO3S/c14-11(15)7-13-12(16)10(8-17)6-9-4-2-1-3-5-9/h1-5,10,17H,6-8H2,(H,13,16)(H,14,15)/f/h13-14H
InChI Key LJJKNPQAGWVLDQ-KGCNKATMCP
KEGG Drug Not Available
KEGG Compound C01619 Link Image
PubChem Compound 3132 Link Image
PubChem Substance 4771 Link Image
ChEBI ID Not Available
PharmGKB ID Not Available
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] Not Available
RxList Link Not Available
PDRhealth Link Not Available
Wikipedia Link Not Available
FDA Label Not Available
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference Not Available
Average Molecular Weight 253.3170
Monoisotopic Molecular Weight 253.0773
State Solid
Melting Point Not Available
Experimental Water Solubility Not Available Source: PhysProp
Predicted Water Solubility 4.45e-01 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity Not Available Source: PhysProp
Predicted LogP 1.78 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -2.76 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID 1DMT Link Image
Experimental PDB File Show
Experimental PDB Structure
Isomeric SMILES OC(=O)CNC(=O)[C@@H](CS)CC1=CC=CC=C1
Canonical SMILES OC(=O)CNC(=O)C(CS)CC1=CC=CC=C1
Drug Category
  • Anti-Arrhythmic Agents
  • Antihypertensive Agents
  • Protease Inhibitors
  • Vasodilator Agents
ATC Codes Not Available
AHFS Codes Not Available
Indication Not Available
Pharmacology Not Available
Mechanism of Action Not Available
Absorption Not Available
Toxicity Not Available
Protein Binding Not Available
Biotransformation Not Available
Half Life Not Available
Dosage Forms Not Available
Patient Information Not Available
Contraindications Not Available
Interactions Not Available
Drug Interactions Not Available
Food Interactions Not Available
Pathways Not Available
General References Not Available
Organisms Affected Not Available
Targets
  1. Neprilysin
Drug Target 1 [top]
Target 1 ID 294
Target 1 Name Neprilysin
Target 1 Synonyms
  1. Atriopeptidase
  2. CALLA
  3. CD10 antigen
  4. Common acute lymphocytic leukemia antigen
  5. EC 3.4.24.11
  6. Enkephalinase
  7. NEP
  8. Neutral endopeptidase
  9. Neutral endopeptidase 24.11
Target 1 Gene Name MME
Target 1 Protein Sequence >Neprilysin 
GKSESQMDITDINTPKPKKKQRWTPLEISLSVLVLLLTIIAVTMIALYATYDDGICKSSD
CIKSAARLIQNMDATTEPCTDFFKYACGGWLKRNVIPETSSRYGNFDILRDELEVVLKDV
LQEPKTEDIVAVQKAKALYRSCINESAIDSRGGEPLLKLLPDIYGWPVATENWEQKYGAS
WTAEKAIAQLNSKYGKKVLINLFVGTDDKNSVNHVIHIDQPRLGLPSRDYYECTGIYKEA
CTAYVDFMISVARLIRQEERLPIDENQLALEMNKVMELEKEIANATAKPEDRNDPMLLYN
KMTLAQIQNNFSLEINGKPFSWLNFTNEIMSTVNISITNEEDVVVYAPEYLTKLKPILTK
YSARDLQNLMSWRFIMDLVSSLSRTYKESRNAFRKALYGTTSETATWRRCANYVNGNMEN
AVGRLYVEAAFAGESKHVVEDLIAQIREVFIQTLDDLTWMDAETKKRAEEKALAIKERIG
YPDDIVSNDNKLNNEYLELNYKEDEYFENIIQNLKFSQSKQLKKLREKVDKDEWISGAAV
VNAFYSSGRNQIVFPAGILQPPFFSAQQSNSLNYGGIGMVIGHEITHGFDDNGRNFNKDG
DLVDWWTQQSASNFKEQSQCMVYQYGNFSWDLAGGQHLNGINTLGENIADNGGLGQAYRA
YQNYIKKNGEEKLLPGLDLNHKQLFFLNFAQVWCGTYRPEYAVNSIKTDVHSPGNFRIIG
TLQNSAEFSEAFHCRKNSYMNPEKKCRVW
Target 1 Number of Residues 761
Target 1 Molecular Weight 85384
Target 1 Theoretical pI 5.43
Target 1 GO Classification
Function
endopeptidase activity
metalloendopeptidase activity
neprilysin activity
binding
ion binding
cation binding
transition metal ion binding
zinc ion binding
catalytic activity
hydrolase activity
peptidase activity
metallopeptidase activity
Process
physiological process
metabolism
macromolecule metabolism
protein metabolism
cellular protein metabolism
proteolysis
Component
cell
membrane
Target 1 General Function Posttranslational modification, protein turnover, chaperones
Target 1 Specific Function Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids. Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond. Involved in the degradation of atrial natriuretic factor (ANF)
Target 1 Pathways Not Available
Target 1 Reactions
  • Preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1' COFACTOR Zinc INHIBITOR EDTA; Phosphoramidon; (S)-N-[3-(3,4-Methylenedioxyphenyl)-2-(mercaptomethyl)-1-oxoprolyl]g lycine; (S)-N-[3-(3,4-Methylenedioxyphenyl)-2-(mercaptomethyl)-1-oxoprolyl]- (S)-alanine; (S)-N-[3-(3,4-Methylenedioxyphenyl)-2-(acetylthio)methyl-1-oxoprolyl ]glycine benzyl ester; (S)-N-[3-(3,4-Methylenedioxyphenyl)-2-(acetylthio)methyl-1-oxoprolyl ]-(S)-alanine benzyl ester; Thiorphan
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 28-50
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 34758 Link Image
Target 1 UniProtKB/Swiss-Prot ID P08473 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name NEP_HUMAN Link Image
Target 1 PDB ID 1DMT Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Membrane
  • single-pass type II membrane protein
Target 1 Gene Sequence >2232 bp 
ATGGATATAACTGATATCAACACTCCAAAGCCAAAGAAGAAACAGCGATGGACTCCACTG
GAGATCAGCCTCTCGGTCCTTGTCCTGCTCCTCACCATCATAGCTGTGACAATGATCGCA
CTCTATGCAACCTACGATGATGGTATTTGCAAGTCATCAGACTGCATAAAATCAGCTGCT
CGACTGATCCAAAACATGGATGCCACCACTGAGCCTTGTACAGACTTTTTCAAATATGCT
TGCGGAGGCTGGTTGAAACGTAATGTCATTCCCGAGACCAGCTCCCGTTACGGCAACTTT
GACATTTTAAGAGATGAACTAGAAGTCGTTTTGAAAGATGTCCTTCAAGAACCCAAAACT
GAAGATATAGTAGCAGTGCAGAAAGCAAAAGCATTGTACAGGTCTTGTATAAATGAATCT
GCTATTGATAGCAGAGGTGGAGAACCTCTACTCAAACTGTTACCAGACATATATGGGTGG
CCAGTAGCAACAGAAAACTGGGAGCAAAAATATGGTGCTTCTTGGACAGCTGAAAAAGCT
ATTGCACAACTGAATTCTAAATATGGGAAAAAAGTCCTTATTAATTTGTTTGTTGGCACT
GATGATAAGAATTCTGTGAATCATGTAATTCATATTGACCAACCTCGACTTGGCCTCCCT
TCTAGAGATTACTATGAATGCACTGGAATCTATAAAGAGGCTTGTACAGCATATGTGGAT
TTTATGATTTCTGTGGCCAGATTGATTCGTCAGGAAGAAAGATTGCCCATCGATGAAAAC
CAGCTTGCTTTGGAAATGAATAAAGTTATGGAATTGGAAAAAGAAATTGCCAATGCTACG
GCTAAACCTGAAGATCGAAATGATCCAATGCTTCTGTATAACAAGATGACATTGGCCCAG
ATCCAAAATAACTTTTCACTAGAGATCAATGGGAAGCCATTCAGCTGGTTGAATTTCACA
AATGAAATCATGTCAACTGTGAATATTAGTATTACAAATGAGGAAGATGTGGTTGTTTAT
GCTCCAGAATATTTAACCAAACTTAAGCCCATTCTTACCAAATATTCTGCCAGAGATCTT
CAAAATTTAATGTCCTGGAGATTCATAATGGATCTTGTAAGCAGCCTCAGCCGAACCTAC
AAGGAGTCCAGAAATGCTTTCCGCAAGGCCCTTTATGGTACAACCTCAGAAACAGCAACT
TGGAGACGTTGTGCAAACTATGTCAATGGGAATATGGAAAATGCTGTGGGGAGGCTTTAT
GTGGAAGCAGCATTTGCTGGAGAGAGTAAACATGTGGTCGAGGATTTGATTGCACAGATC
CGAGAAGTTTTTATTCAGACTTTAGATGACCTCACTTGGATGGATGCCGAGACAAAAAAG
AGAGCTGAAGAAAAGGCCTTAGCAATTAAAGAAAGGATCGGCTATCCTGATGACATTGTT
TCAAATGATAACAAACTGAATAATGAGTACCTCGAGTTGAACTACAAAGAAGATGAATAC
TTCGAGAACATAATTCAAAATTTGAAATTCAGCCAAAGTAAACAACTGAAGAAGCTCCGA
GAAAAGGTGGACAAAGATGAGTGGATAAGTGGAGCAGCTGTAGTCAATGCATTTTACTCT
TCAGGAAGAAATCAGATAGTCTTCCCAGCCGGCATTCTGCAGCCCCCCTTCTTTAGTGCC
CAGCAGTCCAACTCATTGAACTATGGGGGCATCGGCATGGTCATAGGACACGAAATCACC
CATGGCTTCGATGACAATGGCAGAAACTTTAACAAAGATGGAGACCTCGTTGACTGGTGG
ACTCAACAGTCTGCAAGTAACTTTAAGGAGCAATCCCAGTGCATGGTGTATCAGTATGGA
AACTTTTCCTGGGACCTGGCAGGTGGACAGCACCTTAATGGAATTAATACACTGGGAGAA
AACATTGCTGATAATGGAGGTCTTGGTCAAGCATACAGAGCCTATCAGAATTATATTAAA
AAGAATGGCGAAGAAAAATTACTTCCTGGACTTGACCTAAATCACAAACAACTATTTTTC
TTGAACTTTGCACAGGTGTGGTGTGGAACCTATAGGCCAGAGTATGCGGTTAACTCCATT
AAAACAGATGTGCACAGTCCAGGCAATTTCAGGATTATTGGGACTTTGCAGAACTCTGCA
GAGTTTTCAGAAGCCTTTCACTGCCGCAAGAATTCATACATGAATCCAGAAAAGAAGTGC
CGGGTTTGGTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID MME Link Image
Target 1 GenAtlas ID MME Link Image
Target 1 HGNC ID HGNC:7154 Link Image
Target 1 Chromosome Location 3
Target 1 Locus 3q25.1-q25.2
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Oefner C, D'Arcy A, Hennig M, Winkler FK, Dale GE: Structure of human neutral endopeptidase (Neprilysin) complexed with phosphoramidon. J Mol Biol. 2000 Feb 18;296(2):341-9. [PubMed Link Image]
  2. Zhang H, Li XJ, Martin DB, Aebersold R: Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nat Biotechnol. 2003 Jun;21(6):660-6. Epub 2003 May 18. [PubMed Link Image]
  3. D'Adamio L, Shipp MA, Masteller EL, Reinherz EL: Organization of the gene encoding common acute lymphoblastic leukemia antigen (neutral endopeptidase 24.11): multiple miniexons and separate 5' untranslated regions. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7103-7. [PubMed Link Image]
  4. Shipp MA, Richardson NE, Sayre PH, Brown NR, Masteller EL, Clayton LK, Ritz J, Reinherz EL: Molecular cloning of the common acute lymphoblastic leukemia antigen (CALLA) identifies a type II integral membrane protein. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4819-23. [PubMed Link Image]
  5. Letarte M, Vera S, Tran R, Addis JB, Onizuka RJ, Quackenbush EJ, Jongeneel CV, McInnes RR: Common acute lymphocytic leukemia antigen is identical to neutral endopeptidase. J Exp Med. 1988 Oct 1;168(4):1247-53. [PubMed Link Image]
  6. Malfroy B, Kuang WJ, Seeburg PH, Mason AJ, Schofield PR: Molecular cloning and amino acid sequence of human enkephalinase (neutral endopeptidase). FEBS Lett. 1988 Feb 29;229(1):206-10. [PubMed Link Image]
  7. Le Moual H, Dion N, Roques BP, Crine P, Boileau G: Asp650 is crucial for catalytic activity of neutral endopeptidase 24-11. Eur J Biochem. 1994 Apr 1;221(1):475-80. [PubMed Link Image]
Target 1 Drug References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]

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