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Record Information
Version2.0
Creation Date2009-07-30 17:59:02 UTC
Update Date2014-12-24 20:26:07 UTC
Accession NumberT3D3522
Identification
Common Name1,1-Dimethylbiguanide
ClassSmall Molecule
DescriptionMetformin is the most popular anti-diabetic drug in the United States and one of the most prescribed drugs in the country overall, with nearly 35 million prescriptions filled in 2006 for generic metformin alone. Metformin is a biguanide antihyperglycemic agent used for treating non-insulin-dependent diabetes mellitus (NIDDM). It improves glycemic control by decreasing hepatic glucose production, decreasing glucose absorption and increasing insulin-mediated glucose uptake. Metformin is the only oral antihyperglycemic agent that is not associated with weight gain. Metformin may induce weight loss and is the drug of choice for obese NIDDM patients. When used alone, metformin does not cause hypoglycemia; however, it may potentiate the hypoglycemic effects of sulfonylureas and insulin. Its main side effects are dyspepsia, nausea and diarrhea. Dose titration and/or use of smaller divided doses may decrease side effects. Metformin should be avoided in those with severely compromised renal function (creatinine clearance < 30 ml/min), acute/decompensated heart failure, severe liver disease and for 48 hours after the use of iodinated contrast dyes due to the risk of lactic acidosis. Lower doses should be used in the elderly and those with decreased renal function. Metformin decreases fasting plasma glucose, postprandial blood glucose and glycosolated hemoglobin (HbA1c) levels, which are reflective of the last 8-10 weeks of glucose control. Metformin may also have a positive effect on lipid levels. In 2012, a combination tablet of linagliptin plus metformin hydrochloride was marketed under the name Jentadueto for use in patients when treatment with both linagliptin and metformin is appropriate.
Compound Type
  • Amide
  • Amine
  • Antidiabetic Agent
  • Drug
  • Food Toxin
  • Hypoglycemic Agent
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
1,1-Dimethyl biguanide
Apo-Metformin
Diabefagos
Diabex
Diaformin
Dianben
Dimethylbiguanid
Dimethylbiguanide
DMBG
Fortamet
Gen-Metformin
Glucophage
Glucophage XR
Glumetza
Haurymellin
Meguan
Metformin
Metformina
Metformine
Metformine pamoate
Metforminum
Metiguanide
Mylan-Metformin
N,N-Dimethylbiguanide
N,N-Dimethylimidodicarbonimidic diamide
N1,N1-Dimethylbiguanide
Novo-Metformin
Nu-Metformin
Obimet
PMS-Metformin
Ran-Metformin
Ratio-Metformin
Riomet
Sandoz Metformin
Teva-Metformin
Chemical FormulaC4H11N5
Average Molecular Mass129.164 g/mol
Monoisotopic Mass129.101 g/mol
CAS Registry Number657-24-9
IUPAC Name1-carbamimidamido-N,N-dimethylmethanimidamide
Traditional Namemetformin
SMILESCN(C)C(=N)NC(N)=N
InChI IdentifierInChI=1S/C4H11N5/c1-9(2)4(7)8-3(5)6/h1-2H3,(H5,5,6,7,8)
InChI KeyInChIKey=XZWYZXLIPXDOLR-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as biguanides. These are organic compounds containing two N-linked guanidines.
KingdomOrganic compounds
Super ClassOrganic nitrogen compounds
ClassOrganonitrogen compounds
Sub ClassGuanidines
Direct ParentBiguanides
Alternative Parents
Substituents
  • Biguanide
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboximidamide
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Imine
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • Erythrocyte
  • Liver
  • Muscle
  • Skeletal Muscle
PathwaysNot Available
Applications
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point223-226°C
Boiling PointNot Available
SolubilityFreely soluble as HCl salt
LogP-0.5
Predicted Properties
PropertyValueSource
Water Solubility1.38 g/LALOGPS
logP-1.8ALOGPS
logP-0.92ChemAxon
logS-2ALOGPS
pKa (Strongest Basic)12.33ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area88.99 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity56.64 m³·mol⁻¹ChemAxon
Polarizability13.43 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0006-9100000000-4cf43a0a5a8d4db19a46JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-001i-0900000000-9046e2aa0408a0396007JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-01qi-9700000000-a6b98d87cc840a082179JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-00dr-9000000000-8e80f301bad045540477JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positivesplash10-001i-0900000000-bd8aed328c944acd1270JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positivesplash10-03l9-9300000000-3d585674ffe84238e5bfJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positivesplash10-00di-9000000000-ee68820579ebe4d31082JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positivesplash10-00di-9000000000-4312e7e5e1b0dd9ef936JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positivesplash10-00di-9000000000-053d63fe09a95fc1d544JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0229-9100000000-7fe999a9d1aaae3bbe53JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-001i-0900000000-c235cd5d0dda3f3c28d9JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-001i-0900000000-0fa445716bfc24131a75JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-001i-3900000000-dee37da326e6f0b2c56aJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-001i-0900000000-45bd1f8c6d2dc4f38944JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-001i-1900000000-38f3dedb5c19900cdefbJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-001i-7900000000-bf5d1092aa372c303d61JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-03l9-9300000000-06a99f0dff4b41a23cfaJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-022i-9100000000-811c9e7cf8b30b27c0f2JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-00di-9000000000-d34b9b3ab9eb78317ebaJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-001i-0900000000-4d53ac0f7dfaf860e784JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-6900000000-03a99ea4f96636a6d5e2JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0079-9000000000-24ee057ec9505ccf8d3dJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0229-9000000000-bc7faff99aaa83f5e600JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-9300000000-e145cf58ec0f6be503abJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000i-9100000000-0cc6d6ceac8192964ee4JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9000000000-f47eab8fa0fd4177cfddJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureAbsorbed over 6 hours, bioavailability is 50 to 60% under fasting conditions. Administration with food decreases and delays absorption. Some evidence indicates that the level of absorption is not dose-related, suggesting that absorption occurs through a saturable process. Limited data from animal and human cell cultures indicate that absorption occurs through a passive, non-saturable process, possibly involving a paracellular route. Peak action occurs 3 hours after oral administration.
Mechanism of ToxicityMetformin's mechanisms of action differ from other classes of oral antihyperglycemic agents. Metformin decreases blood glucose levels by decreasing hepatic glucose production, decreasing intestinal absorption of glucose, and improving insulin sensitivity by increasing peripheral glucose uptake and utilization. These effects are mediated by the initial activation by metformin of AMP-activated protein kinase (AMPK), a liver enzyme that plays an important role in insulin signaling, whole body energy balance, and the metabolism of glucose and fats. Activation of AMPK is required for metformin's inhibitory effect on the production of glucose by liver cells. Increased peripheral utilization of glucose may be due to improved insulin binding to insulin receptors. Metformin administration also increases AMPK activity in skeletal muscle. AMPK is known to cause GLUT4 deployment to the plasma membrane, resulting in insulin-independent glucose uptake. The rare side effect, lactic acidosis, is thought to be caused by decreased liver uptake of serum lactate, one of the substrates of gluconeogenesis. In those with healthy renal function, the slight excess is simply cleared. However, those with severe renal impairment may accumulate clinically significant serum lactic acid levels. Other conditions that may precipitate lactic acidosis include severe hepatic disease and acute/decompensated heart failure.
MetabolismMetformin is not metabolized. Route of Elimination: Intravenous single-dose studies in normal subjects demonstrate that metformin is excreted unchanged in the urine and does not undergo hepatic metabolism (no metabolites have been identified in humans) nor biliary excretion. Approximately 90% of the drug is eliminated in 24 hours in those with healthy renal function. Renal clearance of metformin is approximately 3.5 times that of creatinine clearance, indicating the tubular secretion is the primary mode of metformin elimination. Half Life: 6.2 hours. Duration of action is 8-12 hours.
Toxicity ValuesAcute oral toxicity (LD50): 350 mg/kg [Rabbit].
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor use as an adjunct to diet and exercise in adult patients (18 years and older) with NIDDM. May also be used for the management of metabolic and reproductive abnormalities associated with polycystic ovary syndrome (PCOS). Jentadueto is for the treatment of patients when both linagliptin and metformin is appropriate.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsAcute oral toxicity (LD50): 350 mg/kg [Rabbit]. It would be expected that adverse reactions of a more intense character including epigastric discomfort, nausea, and vomiting followed by diarrhea, drowsiness, weakness, dizziness, malaise and headache might be seen.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00331
HMDB IDHMDB01921
PubChem Compound ID4091
ChEMBL IDCHEMBL1431
ChemSpider ID3949
KEGG IDC07151
UniProt IDNot Available
OMIM ID125853 , 184700
ChEBI ID6801
BioCyc IDNot Available
CTD IDNot Available
Stitch IDMetformin
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkMetformin
References
Synthesis Reference

Jorn Moeckel, Rolf-Dieter Gabel, Heinrich Woog, “Pharmaceutical preparation containing metformin and a process for producing it.” U.S. Patent US5955106, issued October, 1991.

MSDSLink
General References
  1. Witters LA: The blooming of the French lilac. J Clin Invest. 2001 Oct;108(8):1105-7. [11602616 ]
  2. UNGAR G, FREEDMAN L, SHAPIRO SL: Pharmacological studies of a new oral hypoglycemic drug. Proc Soc Exp Biol Med. 1957 May;95(1):190-2. [13432032 ]
  3. Lord JM, Flight IH, Norman RJ: Metformin in polycystic ovary syndrome: systematic review and meta-analysis. BMJ. 2003 Oct 25;327(7421):951-3. [14576245 ]
  4. Marchesini G, Brizi M, Bianchi G, Tomassetti S, Zoli M, Melchionda N: Metformin in non-alcoholic steatohepatitis. Lancet. 2001 Sep 15;358(9285):893-4. [11567710 ]
  5. Nair S, Diehl AM, Wiseman M, Farr GH Jr, Perrillo RP: Metformin in the treatment of non-alcoholic steatohepatitis: a pilot open label trial. Aliment Pharmacol Ther. 2004 Jul 1;20(1):23-8. [15225167 ]
  6. Seale FG 4th, Robinson RD, Neal GS: Association of metformin and pregnancy in the polycystic ovary syndrome. A report of three cases. J Reprod Med. 2000 Jun;45(6):507-10. [10900588 ]
  7. Briggs GG, Ambrose PJ, Nageotte MP, Padilla G, Wan S: Excretion of metformin into breast milk and the effect on nursing infants. Obstet Gynecol. 2005 Jun;105(6):1437-41. [15932841 ]
  8. De Jager J, Kooy A, Lehert P, Bets D, Wulffele MG, Teerlink T, Scheffer PG, Schalkwijk CG, Donker AJ, Stehouwer CD: Effects of short-term treatment with metformin on markers of endothelial function and inflammatory activity in type 2 diabetes mellitus: a randomized, placebo-controlled trial. J Intern Med. 2005 Jan;257(1):100-9. [15606381 ]
  9. Mughal MA, Jan M, Maheri WM, Memon MY, Ali M: The effect of metformin on glycemic control, serum lipids and lipoproteins in diet alone and sulfonylurea-treated type 2 diabetic patients with sub-optimal metabolic control. J Pak Med Assoc. 2000 Nov;50(11):381-6. [11126815 ]
  10. Einhorn D, Rendell M, Rosenzweig J, Egan JW, Mathisen AL, Schneider RL: Pioglitazone hydrochloride in combination with metformin in the treatment of type 2 diabetes mellitus: a randomized, placebo-controlled study. The Pioglitazone 027 Study Group. Clin Ther. 2000 Dec;22(12):1395-409. [11192132 ]
  11. Robert F, Fendri S, Hary L, Lacroix C, Andrejak M, Lalau JD: Kinetics of plasma and erythrocyte metformin after acute administration in healthy subjects. Diabetes Metab. 2003 Jun;29(3):279-83. [12909816 ]
  12. Radziuk J, Pye S: Hepatic glucose uptake, gluconeogenesis and the regulation of glycogen synthesis. Diabetes Metab Res Rev. 2001 Jul-Aug;17(4):250-72. [11544610 ]
  13. Morin-Papunen LC, Vauhkonen I, Koivunen RM, Ruokonen A, Martikainen HK, Tapanainen JS: Endocrine and metabolic effects of metformin versus ethinyl estradiol-cyproterone acetate in obese women with polycystic ovary syndrome: a randomized study. J Clin Endocrinol Metab. 2000 Sep;85(9):3161-8. [10999803 ]
  14. Musi N, Hirshman MF, Nygren J, Svanfeldt M, Bavenholm P, Rooyackers O, Zhou G, Williamson JM, Ljunqvist O, Efendic S, Moller DE, Thorell A, Goodyear LJ: Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes. 2002 Jul;51(7):2074-81. [12086935 ]
  15. Marathe PH, Wen Y, Norton J, Greene DS, Barbhaiya RH, Wilding IR: Effect of altered gastric emptying and gastrointestinal motility on metformin absorption. Br J Clin Pharmacol. 2000 Oct;50(4):325-32. [11012555 ]
  16. Gore DC, Wolf SE, Sanford A, Herndon DN, Wolfe RR: Influence of metformin on glucose intolerance and muscle catabolism following severe burn injury. Ann Surg. 2005 Feb;241(2):334-42. [15650645 ]
  17. Gillies PS, Dunn CJ: Pioglitazone. Drugs. 2000 Aug;60(2):333-43; discussion 344-5. [10983737 ]
  18. Hale TW, Kristensen JH, Hackett LP, Kohan R, Ilett KF: Transfer of metformin into human milk. Diabetologia. 2002 Nov;45(11):1509-14. Epub 2002 Sep 25. [12436333 ]
  19. Lalau JD, Lacroix C: Measurement of metformin concentration in erythrocytes: clinical implications. Diabetes Obes Metab. 2003 Mar;5(2):93-8. [12630933 ]
  20. Kouki T, Takasu N, Nakachi A, Tamanaha T, Komiya I, Tawata M: Low-dose metformin improves hyperglycaemia related to myotonic dystrophy. Diabet Med. 2005 Mar;22(3):346-7. [15717887 ]
  21. Magalhaes FO, Gouveia LM, Torquato MT, Paccola GM, Piccinato CE, Foss MC: Metformin increases blood flow and forearm glucose uptake in a group of non-obese type 2 diabetes patients. Horm Metab Res. 2006 Aug;38(8):513-7. [16941277 ]
  22. Gore DC, Herndon DN, Wolfe RR: Comparison of peripheral metabolic effects of insulin and metformin following severe burn injury. J Trauma. 2005 Aug;59(2):316-22; discussion 322-3. [16294070 ]
  23. Bridger T, MacDonald S, Baltzer F, Rodd C: Randomized placebo-controlled trial of metformin for adolescents with polycystic ovary syndrome. Arch Pediatr Adolesc Med. 2006 Mar;160(3):241-6. [16520442 ]
  24. Amador-Licona N, Guizar-Mendoza J, Vargas E, Sanchez-Camargo G, Zamora-Mata L: The short-term effect of a switch from glibenclamide to metformin on blood pressure and microalbuminuria in patients with type 2 diabetes mellitus. Arch Med Res. 2000 Nov-Dec;31(6):571-5. [11257323 ]
  25. Carter D, Howlett HC, Wiernsperger NF, Bailey C: Effects of metformin on bile salt transport by monolayers of human intestinal Caco-2 cells. Diabetes Obes Metab. 2002 Nov;4(6):424-7. [12406042 ]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

General Function:
Protein kinase activity
Specific Function:
Non-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Beta non-catalytic subunit acts as a scaffold on which the AMPK complex assembles, via its C-terminus that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1, PRKAG2 or PRKAG3).
Gene Name:
PRKAB1
Uniprot ID:
Q9Y478
Molecular Weight:
30382.085 Da
References
  1. Kovacic S, Soltys CL, Barr AJ, Shiojima I, Walsh K, Dyck JR: Akt activity negatively regulates phosphorylation of AMP-activated protein kinase in the heart. J Biol Chem. 2003 Oct 10;278(41):39422-7. Epub 2003 Jul 29. [12890675 ]
  2. Hardie DG: Minireview: the AMP-activated protein kinase cascade: the key sensor of cellular energy status. Endocrinology. 2003 Dec;144(12):5179-83. Epub 2003 Sep 4. [12960015 ]
  3. Ruderman NB, Saha AK, Kraegen EW: Minireview: malonyl CoA, AMP-activated protein kinase, and adiposity. Endocrinology. 2003 Dec;144(12):5166-71. Epub 2003 Sep 18. [14500570 ]
  4. Leverve XM, Guigas B, Detaille D, Batandier C, Koceir EA, Chauvin C, Fontaine E, Wiernsperger NF: Mitochondrial metabolism and type-2 diabetes: a specific target of metformin. Diabetes Metab. 2003 Sep;29(4 Pt 2):6S88-94. [14502105 ]
  5. Leclerc I, Woltersdorf WW, da Silva Xavier G, Rowe RL, Cross SE, Korbutt GS, Rajotte RV, Smith R, Rutter GA: Metformin, but not leptin, regulates AMP-activated protein kinase in pancreatic islets: impact on glucose-stimulated insulin secretion. Am J Physiol Endocrinol Metab. 2004 Jun;286(6):E1023-31. Epub 2004 Feb 10. [14871885 ]
General Function:
Virus receptor activity
Specific Function:
Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation. When overexpressed, enhanced cell proliferation, a process inhibited by GPC3. Acts also as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline.
Gene Name:
DPP4
Uniprot ID:
P27487
Molecular Weight:
88277.935 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5029 uMNot AvailableBindingDB 50229665
References
  1. Taldone T, Zito SW, Talele TT: Inhibition of dipeptidyl peptidase-IV (DPP-IV) by atorvastatin. Bioorg Med Chem Lett. 2008 Jan 15;18(2):479-84. Epub 2007 Dec 3. [18068977 ]
General Function:
Secondary active organic cation 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:
61153.345 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC502010 uMNot AvailableBindingDB 50229665
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 ]
General Function:
Quaternary ammonium group 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:
62579.99 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC501700 uMNot AvailableBindingDB 50229665
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 ]