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Record Information
Version3.6
Creation Date2012-09-06 15:16:51 UTC
Update Date2016-02-11 01:31:16 UTC
HMDB IDHMDB15050
Secondary Accession NumbersNone
Metabolite Identification
Common NamePhenformin
DescriptionA biguanide hypoglycemic agent with actions and uses similar to those of metformin. Although it is generally considered to be associated with an unacceptably high incidence of lactic acidosis, often fatal, it is still available in some countries. (From Martindale, The Extra Pharmacopoeia, 30th ed, p290)
Structure
Thumb
Synonyms
ValueSource
DBIChEBI
FenforminaChEBI
PhenformineChEBI
PhenforminumChEBI
beta-PebgHMDB
beta-PhenethybiguanideHMDB
beta-PhenethylbiguanideHMDB
FenforminHMDB
N-Phenethylbiguanide hydrochlorideHMDB
PEDGHMDB
Phenethylbiguanide hydrochlorideHMDB
PhenethyldiguanideHMDB
Phenformin HCLHMDB
Phenformin hydrochlorideHMDB
Phenformine HCLHMDB
Phenoformine hydrochlorideHMDB
PhenylethylbiguanideHMDB
Chemical FormulaC10H15N5
Average Molecular Weight205.2596
Monoisotopic Molecular Weight205.132745505
IUPAC Name1-carbamimidamido-N-(2-phenylethyl)methanimidamide
Traditional Namephenethylbiguanide
CAS Registry Number114-86-3
SMILES
NC(=N)NC(=N)NCCC1=CC=CC=C1
InChI Identifier
InChI=1S/C10H15N5/c11-9(12)15-10(13)14-7-6-8-4-2-1-3-5-8/h1-5H,6-7H2,(H6,11,12,13,14,15)
InChI KeyInChIKey=ICFJFFQQTFMIBG-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenethylamines. These are compounds containing a phenethylamine moiety, which consists of a phenyl group substituted at the second position by an ethan-1-amine.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenethylamines
Direct ParentPhenethylamines
Alternative Parents
Substituents
  • Phenethylamine
  • Biguanide
  • Guanidine
  • Carboximidamide
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Imine
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Hypoglycemic Agents
Application
  • Pharmaceutical
Cellular locations
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point175 - 178 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility2.32e-01 g/LNot Available
LogP0.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.23 mg/mLALOGPS
logP-0.72ALOGPS
logP0.83ChemAxon
logS-3ALOGPS
pKa (Strongest Basic)11.97ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area97.78 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity80.72 m3·mol-1ChemAxon
Polarizability22.14 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00914
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00914
  • Not Applicable
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00914
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID7953
KEGG Compound IDC07673
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkPhenformin
NuGOwiki LinkHMDB15050
Metagene LinkHMDB15050
METLIN IDNot Available
PubChem Compound8249
PDB IDNot Available
ChEBI ID382509
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Rosand J, Friedberg JW, Yang JM: Fatal phenformin-associated lactic acidosis. Ann Intern Med. 1997 Jul 15;127(2):170. [9230023 ]
  2. Enia G, Garozzo M, Zoccali C: Lactic acidosis induced by phenformin is still a public health problem in Italy. BMJ. 1997 Nov 29;315(7120):1466-7. [9418116 ]

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. [19934256 ]
General function:
Involved in protein kinase activity
Specific function:
Responsible for the regulation of fatty acid synthesis by phosphorylation of acetyl-CoA carboxylase. It also regulates cholesterol synthesis via phosphorylation and inactivation of hormone-sensitive lipase and hydroxymethylglutaryl-CoA reductase. Appears to act as a metabolic stress-sensing protein kinase switching off biosynthetic pathways when cellular ATP levels are depleted and when 5'-AMP rises in response to fuel limitation and/or hypoxia. This is a catalytic subunit
Gene Name:
PRKAA1
Uniprot ID:
Q13131
Molecular weight:
64008.6
References
  1. Woollhead AM, Sivagnanasundaram J, Kalsi KK, Pucovsky V, Pellatt LJ, Scott JW, Mustard KJ, Hardie DG, Baines DL: Pharmacological activators of AMP-activated protein kinase have different effects on Na+ transport processes across human lung epithelial cells. Br J Pharmacol. 2007 Aug;151(8):1204-15. Epub 2007 Jul 2. [17603555 ]
  2. Chen S, Murphy J, Toth R, Campbell DG, Morrice NA, Mackintosh C: Complementary regulation of TBC1D1 and AS160 by growth factors, insulin and AMPK activators. Biochem J. 2008 Jan 15;409(2):449-59. [17995453 ]
  3. Zhang L, He H, Balschi JA: Metformin and phenformin activate AMP-activated protein kinase in the heart by increasing cytosolic AMP concentration. Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H457-66. Epub 2007 Mar 16. [17369473 ]
General function:
Involved in inward rectifier potassium channel activity
Specific function:
This potassium channel is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by external barium
Gene Name:
KCNJ8
Uniprot ID:
Q15842
Molecular weight:
47967.5
References
  1. Aziz Q, Thomas A, Khambra T, Tinker A: Phenformin has a direct inhibitory effect on the ATP-sensitive potassium channel. Eur J Pharmacol. 2010 May 25;634(1-3):26-32. Epub 2010 Feb 25. [20188727 ]

Transporters

General function:
Involved in ion transmembrane transporter activity
Specific function:
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)- N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin- dependent kinase II and LCK tyrosine kinase
Gene Name:
SLC22A1
Uniprot ID:
O15245
Molecular weight:
61187.4
References
  1. Dresser MJ, Xiao G, Leabman MK, Gray AT, Giacomini KM: Interactions of n-tetraalkylammonium compounds and biguanides with a human renal organic cation transporter (hOCT2). Pharm Res. 2002 Aug;19(8):1244-7. [12240953 ]
  2. Wang DS, Jonker JW, Kato Y, Kusuhara H, Schinkel AH, Sugiyama Y: Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin. J Pharmacol Exp Ther. 2002 Aug;302(2):510-5. [12130709 ]
General function:
Involved in ion transmembrane transporter activity
Specific function:
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity
Gene Name:
SLC22A2
Uniprot ID:
O15244
Molecular weight:
62564.0
References
  1. Dresser MJ, Xiao G, Leabman MK, Gray AT, Giacomini KM: Interactions of n-tetraalkylammonium compounds and biguanides with a human renal organic cation transporter (hOCT2). Pharm Res. 2002 Aug;19(8):1244-7. [12240953 ]