Posted inUncategorized

Phenformin

July 24, 2017
Common Name

Phenformin Description

A 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

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source 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 Formlia

C10H15N5 Average Molecliar Weight

205.2596 Monoisotopic Molecliar Weight

205.132745505 IUPAC Name

1-carbamimidamido-N-(2-phenylethyl)methanimidamide Traditional Name

phenethylbiguanide CAS Registry Number

114-86-3 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 Key

ICFJFFQQTFMIBG-UHFFFAOYSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as biguanides. These are organic compounds containing two N-linked guanidines. Kingdom

Chemical entities Super Class

Organic compounds Class

Organic nitrogen compounds Sub Class

Organonitrogen compounds Direct Parent

Biguanides Alternative Parents

  • Benzene and substituted derivatives
  • Carboximidamides
  • Organopnictogen compounds
  • Imines
  • Hydrocarbon derivatives

    • Substituents

  • Biguanide
  • Benzenoid
  • Monocyclic benzene moiety
  • Carboximidamide
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Imine
  • Aromatic homomonocyclic compound

    • Molecliar Framework

    Aromatic homomonocyclic compounds External Descriptors

  • biguanides (CHEBI:8064 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Hypoglycemic Agents

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting Point175 – 178 °CNot Available Boiling PointNot AvailableNot Available Water Solubility2.32e-01 g/LNot Available LogP0.1Not Available

    Predicted Properties

    Property Value Source 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 Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available

    Biological Properties Cellliar Locations

  • Membrane

    • Biofluid Locations

  • Blood
  • Urine

    • Tissue Location

    Not Available Pathways

    Not Available Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00914

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00914

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB00914 DrugBank Metabolite ID

    Not Available Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    7953 KEGG Compound ID

    C07673 BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Phenformin NuGOwiki Link

    HMDB15050 Metagene Link

    HMDB15050 METLIN ID

    Not Available PubChem Compound

    8249 PDB ID

    Not Available ChEBI ID

    382509

    Product: UNC2882

    References Synthesis Reference Not 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. [PubMed: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. [PubMed: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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. doi: 10.1016/j.ejphar.2010.02.023. Epub 2010 Feb 25. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:12240953 ]

    PMID: 9721015

    Last updated on