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Identification
NameTenofovir
Accession NumberDB00300  (APRD01248)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Tenofovir disoproxil fumarate (a prodrug of tenofovir), marketed by Gilead Sciences under the trade name Viread®, belongs to a class of antiretroviral drugs known as nucleotide analogue reverse transcriptase inhibitors (nRTIs), which block reverse transcriptase, an enzyme crucial to viral production in HIV-infected people. [Wikipedia] In vivo tenofovir disoproxil fumarate is converted to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5’-monophosphate.

Structure
Thumb
Synonyms
(R)-9-(2-phosphonomethoxypropyl)adenine
(R)-PMPA
Anh. tenofovir
Anhydrous tenofovir
Tenofovir
Tenofovir (anh.)
External Identifiers
  • GS-1275
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Vireadtablet300 mgoralGilead Sciences Canada Inc2004-03-15Not applicableCanada
Vireadtablet, coated300 mg/1oralREMEDYREPACK INC.2013-03-282016-03-11Us
Vireadtablet, coated300 mg/1oralAvera Mc Kennan Hospital2015-05-18Not applicableUs
Vireadtablet, coated250 mg/1oralGilead Sciences, Inc.2012-01-18Not applicableUs
Vireadtablet, coated200 mg/1oralGilead Sciences, Inc.2012-01-18Not applicableUs
Vireadtablet, coated150 mg/1oralGilead Sciences, Inc.2012-01-18Not applicableUs
Vireadpowder40 mg/goralGilead Sciences, Inc.2012-01-18Not applicableUs
Vireadtablet, coated300 mg/1oralGilead Sciences, Inc.2001-10-26Not applicableUs
Vireadtablet, coated300 mg/1oralState of Florida DOH Central Pharmacy2009-07-01Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixtures
NameLabellerIngredients
AtriplaBristol Myers Squibb & Gilead Sciences, Llc
CompleraPhysicians Total Care, Inc.
StribildState of Florida DOH Central Pharmacy
TruvadaH.J. Harkins Company, Inc.
Salts
Name/CASStructureProperties
Tenofovir disoproxil fumarate
202138-50-9
Thumb
  • InChI Key: VCMJCVGFSROFHV-WZGZYPNHSA-N
  • Monoisotopic Mass: 635.183987333
  • Average Mass: 635.5149
DBSALT000172
Tenofovir monohydrate
206184-49-8
Thumb
  • InChI Key: PINIEAOMWQJGBW-FYZOBXCZSA-N
  • Monoisotopic Mass: 305.088905633
  • Average Mass: 305.231
DBSALT001819
Categories
UNIIW4HFE001U5
CAS number147127-20-6
WeightAverage: 287.2123
Monoisotopic: 287.078340473
Chemical FormulaC9H14N5O4P
InChI KeySGOIRFVFHAKUTI-ZCFIWIBFSA-N
InChI
InChI=1S/C9H14N5O4P/c1-6(18-5-19(15,16)17)2-14-4-13-7-8(10)11-3-12-9(7)14/h3-4,6H,2,5H2,1H3,(H2,10,11,12)(H2,15,16,17)/t6-/m1/s1
IUPAC Name
({[(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)phosphonic acid
SMILES
C[[email protected]](CN1C=NC2=C1N=CN=C2N)OCP(O)(O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as 6-aminopurines. These are purines that carry an amino group at position 6. Purine is a bicyclic aromatic compound made up of a pyrimidine ring fused to an imidazole ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassImidazopyrimidines
Sub ClassPurines and purine derivatives
Direct Parent6-aminopurines
Alternative Parents
Substituents
  • 6-aminopurine
  • Aminopyrimidine
  • Imidolactam
  • Pyrimidine
  • Primary aromatic amine
  • N-substituted imidazole
  • Heteroaromatic compound
  • Organophosphonic acid derivative
  • Organophosphonic acid
  • Imidazole
  • Azole
  • Azacycle
  • Hydrocarbon derivative
  • Primary amine
  • Organophosphorus compound
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationTenofovir is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients 2 years of age and older. It is also indicated for the treatment of chronic hepatitis B in adults and pediatric patients 12 years of age and older.
PharmacodynamicsTenofovir belongs to a class of antiretroviral drugs known as nucleotide analogue reverse transcriptase inhibitors (NtRTIs), which block reverse transcriptase, an enzyme crucial to viral production in HIV-infected people. Tenofovir is currently in late-stage clinical trials for the treatment of hepatitis B. Tenofovir disoproxil fumarate is an acyclic nucleoside phosphonate diester analog of adenosine monophosphate. Tenofovir requires initial diester hydrolysis for conversion to tenofovir and subsequent phosphorylations by cellular enzymes to form tenofovir diphosphate. Tenofovir diphosphate is a weak inhibitor of mammalian DNA polymerases α, β, and mitochondrial DNA polymerase γ.
Mechanism of actionTenofovir inhibits the activity of HIV reverse transcriptase by competing with the natural substrate deoxyadenosine 5’-triphosphate and, after incorporation into DNA, by DNA chain termination. Specifically, the drugs are analogues of the naturally occurring deoxynucleotides needed to synthesize the viral DNA and they compete with the natural deoxynucleotides for incorporation into the growing viral DNA chain. However, unlike the natural deoxynucleotides substrates, NRTIs and NTRTIs (nucleoside/tide reverse transcriptase inhibitors) lack a 3'-hydroxyl group on the deoxyribose moiety. As a result, following incorporation of an NRTI or an NtRTI, the next incoming deoxynucleotide cannot form the next 5'-3' phosphodiester bond needed to extend the DNA chain. Thus, when an NRTI or NtRTI is incorporated, viral DNA synthesis is halted, a process known as chain termination. All NRTIs and NtRTIs are classified as competitive substrate inhibitors.
Related Articles
AbsorptionTenofovir disoproxil fumarate is the water soluble diester prodrug of the active ingredient tenofoir. The oral bioavailability in fasted patients is approximately 25%. When a single oral dose (300 mg) is given to HIV-1 infected subjects in the fasted state, the maximum serum concentration was achieved in 1.0 ± 0.4 hours (Tmax). Cmax and AUC values are 0.30 ± 0.09 µg/mL and 2.29 ± 0.69 µg∙hr/mL. Administration of food (high fat meal containing 40 to 50% fat) increases the oral bioavailability, with an increase in the AUC of approximately 40%. Cmax is lower in the oral powder, compared to the tablet formulation. However, the mean AUC is similar between the two formulations.
Volume of distribution
  • 1.3 ± 0.6 L/kg [tenofovir 1.0 mg/kg IV]
  • 1.2 ± 0.4 L/kg [tenofovir 3.0 mg/kg IV]
Protein bindingVery low: < 0.7% to human plasma proteins and < 7.2% to serum proteins
Metabolism

The cytochrome P450 enzyme system is not involved with the metabolism of tenofovir disoproxil or tenofovir.

SubstrateEnzymesProduct
Tenofovir
Tenofovir MonophosphateDetails
Tenofovir Monophosphate
Tenofovir DiphosphateDetails
Route of eliminationWhen tenofovir is given IV, 70-80% of the dose is recovered in the urine as unchanged drug within 72 hours of administration. Tenofovir is eliminated by a combination of glomerular filtration and active tubular secretion. There may be competition for elimination with other compounds that are also renally eliminated.
Half lifeWhen a single oral dose is given, the terminal elimination half-life is approximately 17 hours.
Clearance

The following are renal clearance (CL renal) parameters for subjects with varying degrees of renal function:

  • 243.5 ± 33.3 mL/min [baseline creatinine clearance >80 mL/min]
  • 168.6 ± 27.5 mL/min [baseline creatinine clearance 50-80 mL/min]
  • 100.6 ± 27.5 mL/min [baseline creatinine clearance 30-49 mL/min]
  • 43.0 ± 31.2 mL/min [baseline creatinine clearance 12-29 mL/min]
    The following are clearance (CL/F) parameters for subjects with varying degrees of renal function:
  • 1043.7 ± 115.4 [baseline creatinine clearance >80 mL/min]
  • 807.7 ± 279.2 [baseline creatinine clearance 50-80 mL/min]
  • 444.4 ± 209.8 [baseline creatinine clearance 30-49 mL/min]
  • 177.0 ± 97.1 [baseline creatinine clearance 12-29 mL/min]
ToxicityLimited clinical experience at doses higher than the therapeutic dose of tenofovir 300 mg is available. In Study 901 tenofovir disoproxil fumarate 600 mg was administered to 8 patients orally for 28 days. No severe adverse reactions were reported. The effects of higher doses are not known.
Affected organisms
  • Human Immunodeficiency Virus
Pathways
PathwayCategorySMPDB ID
Tenofovir Metabolism PathwayDrug metabolismSMP00630
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.5998
Blood Brain Barrier+0.9194
Caco-2 permeable-0.617
P-glycoprotein substrateSubstrate0.7203
P-glycoprotein inhibitor INon-inhibitor0.8706
P-glycoprotein inhibitor IINon-inhibitor0.948
Renal organic cation transporterNon-inhibitor0.8985
CYP450 2C9 substrateNon-substrate0.8609
CYP450 2D6 substrateNon-substrate0.9117
CYP450 3A4 substrateNon-substrate0.6458
CYP450 1A2 substrateNon-inhibitor0.7177
CYP450 2C9 inhibitorNon-inhibitor0.7873
CYP450 2D6 inhibitorNon-inhibitor0.8271
CYP450 2C19 inhibitorNon-inhibitor0.7634
CYP450 3A4 inhibitorNon-inhibitor0.8353
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.85
Ames testNon AMES toxic0.511
CarcinogenicityNon-carcinogens0.7811
BiodegradationNot ready biodegradable0.9914
Rat acute toxicity2.4903 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8936
hERG inhibition (predictor II)Non-inhibitor0.7957
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Gilead sciences inc
  • Gilead Sciences, Inc.
Packagers
Dosage forms
FormRouteStrength
Tablet, film coatedoral
Tabletoral
Powderoral40 mg/g
Tabletoral300 mg
Tablet, coatedoral150 mg/1
Tablet, coatedoral200 mg/1
Tablet, coatedoral250 mg/1
Tablet, coatedoral300 mg/1
Prices
Unit descriptionCostUnit
Viread 300 mg tablet33.95USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2261619 No2006-05-232017-07-25Canada
CA2298059 No2008-12-302018-07-23Canada
US5814639 Yes1996-03-292016-03-29Us
US5914331 Yes1998-01-022018-01-02Us
US5922695 Yes1998-01-252018-01-25Us
US5935946 Yes1998-01-252018-01-25Us
US5977089 Yes1998-01-252018-01-25Us
US6043230 Yes1998-01-252018-01-25Us
US6639071 Yes1998-08-142018-08-14Us
US6642245 Yes2001-05-042021-05-04Us
US6703396 Yes2001-09-092021-09-09Us
US6838464 No2001-02-262021-02-26Us
US6939964 Yes1998-07-202018-07-20Us
US7067522 No1999-12-202019-12-20Us
US7125879 No2002-08-092022-08-09Us
US7176220 No2003-11-202023-11-20Us
US7635704 No2006-10-262026-10-26Us
US8080551 No2003-04-112023-04-11Us
US8101629 No2002-08-092022-08-09Us
US8148374 No2009-09-032029-09-03Us
US8592397 No2004-01-132024-01-13Us
US8598185 No2008-05-012028-05-01Us
US8633219 No2010-04-242030-04-24Us
US8716264 No2004-01-132024-01-13Us
US8841310 No2005-12-092025-12-09Us
US8981103 No2006-10-262026-10-26Us
US9018192 No2006-06-132026-06-13Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point276-280 °CNot Available
water solubility13.4 mg/mL in distilled water at 25 °C (disoproxil fumarate salt)FDA label
logP1.25FDA label
Predicted Properties
PropertyValueSource
Water Solubility1.87 mg/mLALOGPS
logP-1.5ALOGPS
logP-3.7ChemAxon
logS-2.2ALOGPS
pKa (Strongest Acidic)1.35ChemAxon
pKa (Strongest Basic)5.12ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area136.38 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity67.53 m3·mol-1ChemAxon
Polarizability25.54 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
References
Synthesis Reference

Uma Maheswer Rao Vasireddy, Siva Rama Prasad Vellanki, Raja Babu Balusu, Naga Durga Rao Bandi, Pavan Kumar Jujjavarapu, Sambasiva Rao Ginjupalli, Rama Krishna Pilli, “Process for the preparation of Tenofovir.” U.S. Patent US08049009, issued November 01, 2011.

US08049009
General References
  1. Gilden D: Tenofovir: Gilead applies for approval; expanded access liberalized. AIDS Treat News. 2001 May 11;(364):2-3, 1. [PubMed:11569959 ]
  2. Miller MD, Margot NA, Hertogs K, Larder B, Miller V: Antiviral activity of tenofovir (PMPA) against nucleoside-resistant clinical HIV samples. Nucleosides Nucleotides Nucleic Acids. 2001 Apr-Jul;20(4-7):1025-8. [PubMed:11562951 ]
  3. Thompson CA: Prodrug of tenofovir diphosphate approved for combination HIV therapy. Am J Health Syst Pharm. 2002 Jan 1;59(1):18. [PubMed:11813460 ]
  4. Gazzard BG: The potential place of tenofovir in antiretroviral treatment regimens. Int J Clin Pract. 2001 Dec;55(10):704-9. [PubMed:11777298 ]
  5. Lu C, Jia Y, Chen L, Ding Y, Yang J, Chen M, Song Y, Sun X, Wen A: Pharmacokinetics and food interaction of a novel prodrug of tenofovir, tenofovir dipivoxil fumarate, in healthy volunteers. J Clin Pharm Ther. 2013 Apr;38(2):136-40. doi: 10.1111/jcpt.12023. Epub 2012 Dec 28. [PubMed:23278367 ]
  6. Maskew M, Westreich D, Firnhaber C, Sanne I: Tenofovir use and pregnancy among women initiating HAART. AIDS. 2012 Nov 28;26(18):2393-7. doi: 10.1097/QAD.0b013e328359a95c. [PubMed:22951630 ]
  7. Uglietti A, Zanaboni D, Gnarini M, Maserati R: Emtricitabine/tenofovir in the treatment of HIV infection: current PK/PD evaluation. Expert Opin Drug Metab Toxicol. 2012 Oct;8(10):1305-14. doi: 10.1517/17425255.2012.714367. Epub 2012 Sep 4. [PubMed:22943210 ]
  8. Ransom CE, Huo Y, Patel K, Scott GB, Watts HD, Williams P, Siberry GK, Livingston EG: Infant growth outcomes after maternal tenofovir disoproxil fumarate use during pregnancy. J Acquir Immune Defic Syndr. 2013 Dec 1;64(4):374-81. doi: 10.1097/QAI.0b013e3182a7adb2. [PubMed:24169122 ]
External Links
ATC CodesNot Available
AHFS Codes
  • 08:18.08.20
PDB EntriesNot Available
FDA labelDownload (287 KB)
MSDSDownload (57.7 KB)
Interactions
Drug Interactions
Drug
AciclovirAciclovir may decrease the excretion rate of Tenofovir which could result in a lower serum level and potentially a reduction in efficacy.
Adefovir DipivoxilThe therapeutic efficacy of Tenofovir can be decreased when used in combination with Adefovir Dipivoxil.
AmikacinThe serum concentration of Amikacin can be increased when it is combined with Tenofovir.
ArbekacinThe serum concentration of Arbekacin can be increased when it is combined with Tenofovir.
AtazanavirThe serum concentration of Atazanavir can be decreased when it is combined with Tenofovir.
CelecoxibThe risk or severity of adverse effects can be increased when Celecoxib is combined with Tenofovir.
CidofovirCidofovir may decrease the excretion rate of Tenofovir which could result in a lower serum level and potentially a reduction in efficacy.
CobicistatThe risk or severity of adverse effects can be increased when Cobicistat is combined with Tenofovir.
DarunavirThe serum concentration of Darunavir can be increased when it is combined with Tenofovir.
DiclofenacThe risk or severity of adverse effects can be increased when Diclofenac is combined with Tenofovir.
DidanosineThe therapeutic efficacy of Didanosine can be decreased when used in combination with Tenofovir.
DiflunisalThe risk or severity of adverse effects can be increased when Diflunisal is combined with Tenofovir.
EtodolacThe risk or severity of adverse effects can be increased when Etodolac is combined with Tenofovir.
FenoprofenThe risk or severity of adverse effects can be increased when Fenoprofen is combined with Tenofovir.
FloctafenineThe risk or severity of adverse effects can be increased when Floctafenine is combined with Tenofovir.
FlurbiprofenThe risk or severity of adverse effects can be increased when Flurbiprofen is combined with Tenofovir.
FramycetinThe serum concentration of Framycetin can be increased when it is combined with Tenofovir.
GanciclovirThe serum concentration of Tenofovir can be increased when it is combined with Ganciclovir.
GentamicinThe serum concentration of Gentamicin can be increased when it is combined with Tenofovir.
IbuprofenThe risk or severity of adverse effects can be increased when Ibuprofen is combined with Tenofovir.
IndomethacinThe risk or severity of adverse effects can be increased when Indomethacin is combined with Tenofovir.
InfliximabThe risk or severity of adverse effects can be increased when Infliximab is combined with Tenofovir.
KanamycinThe serum concentration of Kanamycin can be increased when it is combined with Tenofovir.
KetoprofenThe risk or severity of adverse effects can be increased when Ketoprofen is combined with Tenofovir.
KetorolacThe risk or severity of adverse effects can be increased when Ketorolac is combined with Tenofovir.
LedipasvirThe serum concentration of Tenofovir can be increased when it is combined with Ledipasvir.
LopinavirLopinavir may increase the nephrotoxic activities of Tenofovir.
Mefenamic acidThe risk or severity of adverse effects can be increased when Mefenamic acid is combined with Tenofovir.
MeloxicamThe risk or severity of adverse effects can be increased when Meloxicam is combined with Tenofovir.
NabumetoneThe risk or severity of adverse effects can be increased when Nabumetone is combined with Tenofovir.
NaproxenThe risk or severity of adverse effects can be increased when Naproxen is combined with Tenofovir.
NeomycinThe serum concentration of Neomycin can be increased when it is combined with Tenofovir.
NetilmicinThe serum concentration of Netilmicin can be increased when it is combined with Tenofovir.
OxaprozinThe risk or severity of adverse effects can be increased when Oxaprozin is combined with Tenofovir.
PiroxicamThe risk or severity of adverse effects can be increased when Piroxicam is combined with Tenofovir.
RibostamycinThe serum concentration of Ribostamycin can be increased when it is combined with Tenofovir.
SimeprevirThe serum concentration of Simeprevir can be decreased when it is combined with Tenofovir.
SpectinomycinThe serum concentration of Spectinomycin can be increased when it is combined with Tenofovir.
StreptomycinThe serum concentration of Streptomycin can be increased when it is combined with Tenofovir.
SulindacThe risk or severity of adverse effects can be increased when Sulindac is combined with Tenofovir.
TelaprevirThe serum concentration of Tenofovir can be increased when it is combined with Telaprevir.
Tiaprofenic acidThe risk or severity of adverse effects can be increased when Tiaprofenic acid is combined with Tenofovir.
TipranavirThe serum concentration of Tipranavir can be decreased when it is combined with Tenofovir.
TizanidineThe serum concentration of Tizanidine can be increased when it is combined with Tenofovir.
TobramycinThe serum concentration of Tobramycin can be increased when it is combined with Tenofovir.
TolmetinThe risk or severity of adverse effects can be increased when Tolmetin is combined with Tenofovir.
ValaciclovirValaciclovir may decrease the excretion rate of Tenofovir which could result in a lower serum level and potentially a reduction in efficacy.
ValganciclovirThe serum concentration of Tenofovir can be increased when it is combined with Valganciclovir.
Food Interactions
  • When given with a high-fat meal, the oral bioavailability, AUC, and Cmax increased.

Targets

Kind
Protein
Organism
Human immunodeficiency virus 1
Pharmacological action
yes
Actions
inhibitor
General Function:
Rna-dna hybrid ribonuclease activity
Specific Function:
Not Available
Gene Name:
pol
Uniprot ID:
Q72547
Molecular Weight:
65223.615 Da
References
  1. Fung HB, Stone EA, Piacenti FJ: Tenofovir disoproxil fumarate: a nucleotide reverse transcriptase inhibitor for the treatment of HIV infection. Clin Ther. 2002 Oct;24(10):1515-48. [PubMed:12462284 ]
  2. DeChristoforo R, Penzak SR: Tenofovir: a nucleotide analogue reverse-transcriptase inhibitor for treatment of HIV infection. Am J Health Syst Pharm. 2004 Jan 1;61(1):86-98; quiz 99-100. [PubMed:14725126 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Atp binding
Specific Function:
Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP. Plays an important role in cellular energy homeostasis and in adenine nucleotide metabolism. Adenylate kinase activity is critical for regulation of the phosphate utilization and the AMP de novo biosynthesis pathways. Plays a key role in hematopoiesis.
Gene Name:
AK2
Uniprot ID:
P54819
Molecular Weight:
26477.44 Da
References
  1. Antoniou T, Park-Wyllie LY, Tseng AL: Tenofovir: a nucleotide analog for the management of human immunodeficiency virus infection. Pharmacotherapy. 2003 Jan;23(1):29-43. [PubMed:12523458 ]
  2. Link [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Nucleoside triphosphate adenylate kinase activity
Specific Function:
Involved in maintaining the homeostasis of cellular nucleotides by catalyzing the interconversion of nucleoside phosphates. Efficiently phosphorylates AMP and dAMP using ATP as phosphate donor, but phosphorylates only AMP when using GTP as phosphate donor. Also displays broad nucleoside diphosphate kinase activity.
Gene Name:
AK4
Uniprot ID:
P27144
Molecular Weight:
25267.83 Da
References
  1. Antoniou T, Park-Wyllie LY, Tseng AL: Tenofovir: a nucleotide analog for the management of human immunodeficiency virus infection. Pharmacotherapy. 2003 Jan;23(1):29-43. [PubMed:12523458 ]
  2. Link [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Ribosomal small subunit binding
Specific Function:
Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate. Possesses nucleoside-diphosphate kinase, serine/threonine-specific protein kinase, geranyl and farnesyl pyrophosphate kinase, histidine protein kinase and 3'-5' exonuclease activities....
Gene Name:
NME1
Uniprot ID:
P15531
Molecular Weight:
17148.635 Da
References
  1. Link [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Transcription factor activity, sequence-specific dna binding
Specific Function:
Major role in the synthesis of nucleoside triphosphates other than ATP. Negatively regulates Rho activity by interacting with AKAP13/LBC. Acts as a transcriptional activator of the MYC gene; binds DNA non-specifically (PubMed:8392752). Exhibits histidine protein kinase activity.
Gene Name:
NME2
Uniprot ID:
P22392
Molecular Weight:
17297.935 Da
References
  1. Link [Link]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS) (By similarity). Mediates the sodium-in...
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
Molecular Weight:
61815.78 Da
References
  1. Cihlar T, Ho ES, Lin DC, Mulato AS: Human renal organic anion transporter 1 (hOAT1) and its role in the nephrotoxicity of antiviral nucleotide analogs. Nucleosides Nucleotides Nucleic Acids. 2001 Apr-Jul;20(4-7):641-8. [PubMed:11563082 ]
  2. Uwai Y, Ida H, Tsuji Y, Katsura T, Inui K: Renal transport of adefovir, cidofovir, and tenofovir by SLC22A family members (hOAT1, hOAT3, and hOCT2). Pharm Res. 2007 Apr;24(4):811-5. Epub 2007 Feb 15. [PubMed:17372702 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA).
Gene Name:
SLC22A8
Uniprot ID:
Q8TCC7
Molecular Weight:
59855.585 Da
References
  1. Uwai Y, Ida H, Tsuji Y, Katsura T, Inui K: Renal transport of adefovir, cidofovir, and tenofovir by SLC22A family members (hOAT1, hOAT3, and hOCT2). Pharm Res. 2007 Apr;24(4):811-5. Epub 2007 Feb 15. [PubMed:17372702 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Atpase activity, coupled to transmembrane movement of substances
Specific Function:
ATP-dependent transporter probably involved in cellular detoxification through lipophilic anion extrusion.
Gene Name:
ABCC10
Uniprot ID:
Q5T3U5
Molecular Weight:
161627.375 Da
References
  1. Pushpakom SP, Liptrott NJ, Rodriguez-Novoa S, Labarga P, Soriano V, Albalater M, Hopper-Borge E, Bonora S, Di Perri G, Back DJ, Khoo S, Pirmohamed M, Owen A: Genetic variants of ABCC10, a novel tenofovir transporter, are associated with kidney tubular dysfunction. J Infect Dis. 2011 Jul 1;204(1):145-53. doi: 10.1093/infdis/jir215. [PubMed:21628669 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Atpase activity, coupled to transmembrane movement of substances
Specific Function:
May be an organic anion pump relevant to cellular detoxification.
Gene Name:
ABCC4
Uniprot ID:
O15439
Molecular Weight:
149525.33 Da
References
  1. Imaoka T, Kusuhara H, Adachi M, Schuetz JD, Takeuchi K, Sugiyama Y: Functional involvement of multidrug resistance-associated protein 4 (MRP4/ABCC4) in the renal elimination of the antiviral drugs adefovir and tenofovir. Mol Pharmacol. 2007 Feb;71(2):619-27. Epub 2006 Nov 16. [PubMed:17110501 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Organic anion transmembrane transporter activity
Specific Function:
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name:
ABCC2
Uniprot ID:
Q92887
Molecular Weight:
174205.64 Da
References
  1. Izzedine H, Hulot JS, Villard E, Goyenvalle C, Dominguez S, Ghosn J, Valantin MA, Lechat P, Deray AG: Association between ABCC2 gene haplotypes and tenofovir-induced proximal tubulopathy. J Infect Dis. 2006 Dec 1;194(11):1481-91. Epub 2006 Oct 26. [PubMed:17083032 ]
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Drug created on June 13, 2005 07:24 / Updated on June 28, 2016 03:06