Details of the Drug

General Information of Drug (ID: DME8G1U)

Drug Name
L-methionine
Synonyms Acimethin; Cymethion
Indication
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [1]
Drug Type
Small molecular drug
Structure
3D MOL is unavailable 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 149.21
Logarithm of the Partition Coefficient (xlogp) -1.9
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 4
ADMET Property
Absorption
The drug is absorbed from the lumen of the small intestine into the enterocytes by an active transport process []
Metabolism
The drug is metabolized via the hepatic []
Chemical Identifiers
Formula
C5H11NO2S
IUPAC Name
(2S)-2-amino-4-methylsulfanylbutanoic acid
Canonical SMILES
CSCC[C@@H](C(=O)O)N
InChI
InChI=1S/C5H11NO2S/c1-9-3-2-4(6)5(7)8/h4H,2-3,6H2,1H3,(H,7,8)/t4-/m0/s1
InChIKey
FFEARJCKVFRZRR-BYPYZUCNSA-N
Cross-matching ID
PubChem CID
6137
ChEBI ID
CHEBI:16643
CAS Number
63-68-3
DrugBank ID
DB00134
TTD ID
D0PO8E
INTEDE ID
DR1043

Molecular Interaction Atlas of This Drug


Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Methionine-tRNA ligase mitochondrial (MARS2) DEEH5Y9 SYMM_HUMAN Substrate [2]
Peptide methionine sulfoxide reductase (MSRA) DEU2ZBY MSRA_HUMAN Substrate [3]
S-adenosylmethionine synthase 2 (MAT2A) DE76G8C METK2_HUMAN Substrate [4]
Methionine adenosyltransferase II beta (MAT2B) DEKF1OH MAT2B_HUMAN Substrate [2]
S-adenosylmethionine synthase 1 (MAT1A) DEQ6NC9 METK1_HUMAN Substrate [4]
Methionine-R-sulfoxide reductase B1 (MSRB1) DEFADPU MSRB1_HUMAN Substrate [5]
Methionine-R-sulfoxide reductase B2 (MSRB2) DEMQOF7 MSRB2_HUMAN Substrate [6]
Homoserine-O-transsuccinylase (metAA) DER6EU8 METAA_THEMA Substrate [7]
Methionine-tRNA ligase cytoplasmic (MARS) DE0K52I SYMC_HUMAN Substrate [8]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Amino acid transporter heavy chain SLC3A1 (SLC3A1) OT56V01A SLC31_HUMAN Regulation of Drug Effects [9]
Kynurenine--oxoglutarate transaminase 1 (KYAT1) OTRD3RUJ KAT1_HUMAN Biotransformations [10]
Large neutral amino acids transporter small subunit 2 (SLC7A8) OT8XXVO8 LAT2_HUMAN Regulation of Drug Effects [11]
Mitogen-activated protein kinase 8 (MAPK8) OTEREYS5 MK08_HUMAN Gene/Protein Processing [12]
von Willebrand factor OTNMMA2P VWF_HUMAN Protein Interaction/Cellular Processes [13]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from L-methionine (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Ephedrine DMMV0KW Minor as urine pH determines the ionization state of weakly acidic or weakly alkaline drugs. L-methionine caused by Ephedrine mediated altered urine pH. Asthma [CA23] [14]
Pseudoephedrine DMIVJ0D Minor as urine pH determines the ionization state of weakly acidic or weakly alkaline drugs. L-methionine caused by Pseudoephedrine mediated altered urine pH. Breathing abnormality [MD11] [14]
Mexiletine DMCTE9R Minor as urine pH determines the ionization state of weakly acidic or weakly alkaline drugs. L-methionine caused by Mexiletine mediated altered urine pH. Ventricular tachyarrhythmia [BC71] [15]
Flecainide DMSQDLE Minor as urine pH determines the ionization state of weakly acidic or weakly alkaline drugs. L-methionine caused by Flecainide mediated altered urine pH. Ventricular tachyarrhythmia [BC71] [16]

References

1 URL: 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. (Ligand id: 4814).
2 How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
3 Characterization of the amino acids involved in substrate specificity of methionine sulfoxide reductase A. J Biol Chem. 2007 Jul 13;282(28):20484-91.
4 Role of methionine adenosyltransferase 2A and S-adenosylmethionine in mitogen-induced growth of human colon cancer cells. Gastroenterology. 2007 Jul;133(1):207-18.
5 Catalytic advantages provided by selenocysteine in methionine-S-sulfoxide reductases. Biochemistry. 2006 Nov 21;45(46):13697-704.
6 The X-ray structure of the N-terminal domain of PILB from Neisseria meningitidis reveals a thioredoxin-fold. J Mol Biol. 2006 Apr 28;358(2):443-54.
7 Regulation of the methionine feedback-sensitive enzyme in mutants of Salmonella typhimurium. J Bacteriol. 1972 Jan;109(1):8-11.
8 Mutations in methylenetetrahydrofolate reductase or cystathionine beta-synthase gene, or a high-methionine diet, increase homocysteine thiolactone levels in humans and mice. FASEB J. 2007 Jun;21(8):1707-13.
9 Characteristics of transport of selenoamino acids by epithelial amino acid transporters. Chem Biol Interact. 2009 Feb 12;177(3):234-41. doi: 10.1016/j.cbi.2008.09.008. Epub 2008 Sep 19.
10 New insights into the metabolism of organomercury compounds: mercury-containing cysteine S-conjugates are substrates of human glutamine transaminase K and potent inactivators of cystathionine gama-lyase. Arch Biochem Biophys. 2012 Jan 1;517(1):20-9.
11 Methylmercury Uptake into BeWo Cells Depends on LAT2-4F2hc, a System L Amino Acid Transporter. Int J Mol Sci. 2017 Aug 8;18(8):1730. doi: 10.3390/ijms18081730.
12 Methionine restriction induces apoptosis of prostate cancer cells via the c-Jun N-terminal kinase-mediated signaling pathway. Cancer Lett. 2002 May 8;179(1):51-8. doi: 10.1016/s0304-3835(01)00852-7.
13 von Willebrand factor multimer composition is modified following oral methionine load in women with thrombosis, but not in healthy women. Blood Coagul Fibrinolysis. 2005 Jun;16(4):267-73. doi: 10.1097/01.mbc.0000169219.93054.92.
14 Brater DC, Kaojarern S, Benet LZ, et al "Renal excretion of pseudoephedrine." Clin Pharmacol Ther 28 (1980): 690-4. [PMID: 7438686]
15 Mitchell BG, Clements JA, Pottage A, Prescott LF "Mexiletine disposition: individual variation in response to urine acidification and alkalinisation." Br J Clin Pharmacol 16 (1983): 281-4. [PMID: 6626420]
16 Hertrampf R, Gundert-Remy U, Beckmann J, et al "Elimination of flecainide as a function of urinary flow rate and pH." Eur J Clin Pharmacol 41 (1991): 61-3. [PMID: 1782979]