Tenofovir
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Identification
- Summary
Tenofovir is a nucleotide analog indicated in the treatment of HIV infections.
- Generic Name
- Tenofovir
- DrugBank Accession Number
- DB14126
- Background
Tenofovir is an acyclic nucleotide diester analog of adenosine monophosphate.4 In the most strict sense and due to the fact that it presents a phosphate group bound to the nitrogenous base, it is determined as an actual nucleotide analog.4 The antiviral activities of tenofovir were first reported in 1993 and this agent was commercially available since 2008 in the form of tenofovir disoproxil and tenofovir alafenamide in order to obtain oral bioavailability.3,6
- Type
- Small Molecule
- Groups
- Experimental, Investigational
- Structure
- Weight
- Average: 287.2123
Monoisotopic: 287.078340473 - Chemical Formula
- C9H14N5O4P
- Synonyms
- (R)-PMPA
- Anhydrous tenofovir
- Tenofovir
- Tenofovir (anh.)
- Tenofovir (anhydrous)
- Tenofovir anhydrous
- External IDs
- GS 1275
- GS-1275
Pharmacology
- Indication
Tenofovir has been shown to be effective against HIV, herpes simplex virus-2, and hepatitis B virus.5
To know more about the specific product indications, please visit the information in the orally available forms of tenofovir, tenofovir alafenamide and tenofovir disoproxil.
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- Pharmacodynamics
Tenofovir has been shown to be highly effective in patients that have never had an antiretroviral therapy and it seemed to have lower toxicity than other antivirals such as stavudine. In phase 3 clinical trials, tenofovir presented a similar efficacy than efavirenz in treatment-naive HIV patients.5 In hepatitis B infected patients, after one year of tenofovir treatment, the viral DNA levels were undetectable.6
- Mechanism of action
Once tenofovir is activated by a bi-phosphorylation it acts as an antiviral acyclic nucleoside phosphonate. It is a potent inhibitor of the viral reverse transcriptase with an inhibitory constant of approximately 0.022 micromolar.3
Once activated, tenofovir acts with different mechanisms including the inhibition of viral polymerase causing chain termination and the inhibition of viral synthesis.12 All these activities are attained by its competition with deoxyadenosine 5'-triphosphate in the generation of new viral DNA. Once tenofovir is incorporated in the chain, it induces a chain termination which in order inhibits viral replication.5 The safety of tenofovir relies on its low affinity towards the cellular DNA polymerase including the mitochondrial DNA polymerase gamma.11
Target Actions Organism AReverse transcriptase/RNaseH inhibitorHuman immunodeficiency virus 1 AGag-Pol polyprotein inhibitorAReverse transcriptase inhibitorHBV ADNA polymerase inhibitorHuman herpesvirus 2 (strain 186) - Absorption
Tenofovir as the active moiety presents a very low bioavailability when orally administered. Hence, the administration of this active agent is required to be under its two prodrug forms, tenofovir disoproxil and tenofovir alafenamide. This reduced absorption is suggested to be related to the presence of two negative charges among its structure. This negative charge limits its cellular penetration, and its passive diffusion across cellular membranes and intestinal mucosa hindering its availability for oral administration.1
Intravenous tenofovir has been shown to produce a maximum plasma concentration of 2500 ng/ml with an AUC of 4800 ng.h/ml.3
- Volume of distribution
Accumulation of tenofovir in plasma is related to the presence of nephrotoxic effects.1 It is reported that tenofovir presents a volume of distribution of 0.813 L/kg.7
- Protein binding
Tenofovir is minimally bound to plasma proteins and only about 7.2% of the administered dose is found in the bound state.7
- Metabolism
Tenofovir activation is performed by a bi-phosphorylation which in order forms the biologically active compound, tenofovir biphosphate.1 This metabolic activation has been shown to be performed in hepG2 cells and human hepatocytes.8
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- Route of elimination
Tenofovir is eliminated in the urine by tubular secretion and glomerular filtration. The elimination of this compound is driven by the activity of the human organic anion transporters 1 and 3 and its secretion is mainly ruled by the activity of the multidrug resistance-associated protein 4.1
- Half-life
The reported half-life of tenofovir is of 32 hours.2
- Clearance
The clearance of tenofovir is highly dependent on the patient renal stage and hence the clearance rate in patients with renal impairment is reported to be of 134 ml/min while in patients with normal function the clearance rate can be of 210 ml/min.9
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
There haven't been reports regarding the LD50 of the parent compound nor the effects of an overdose. However, based on the reports with the derivative that most rapidly transforms into tenofovir, tenofovir disoproxil, it is recommended to monitor overdose patients. As well, it is widely known that tenofovir is efficiently removed by hemodialysis.10
Administration of high doses of tenofovir has been reported to produce bone toxicity reported as osteomalacia and reduced bone mineral density and to produce some degree of renal toxicity.14
To know more about the carcinogenicity and mutagenic potential of tenofovir, as well as the effect on fertility, please visit the drug entries for the derivatives tenofovir disoproxil and tenofovir alafenamide.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Tenofovir may decrease the excretion rate of Abacavir which could result in a higher serum level. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Tenofovir. Abrocitinib The serum concentration of Tenofovir can be increased when it is combined with Abrocitinib. Aceclofenac Aceclofenac may increase the nephrotoxic activities of Tenofovir. Acemetacin Acemetacin may increase the nephrotoxic activities of Tenofovir. - Food Interactions
- Take with food.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Tenofovir hydrate 99YXE507IL 206184-49-8 PINIEAOMWQJGBW-FYZOBXCZSA-N
Categories
- Drug Categories
- Anti-HIV Agents
- Anti-Infective Agents
- Anti-Retroviral Agents
- Antiviral Agents
- Drugs that are Mainly Renally Excreted
- Enzyme Inhibitors
- Hepatitis B Virus Nucleoside Analog Reverse Transcriptase Inhibitor
- Heterocyclic Compounds, Fused-Ring
- Human Immunodeficiency Virus Nucleoside Analog Reverse Transcriptase Inhibitor
- Nephrotoxic agents
- Nucleic Acid Synthesis Inhibitors
- Nucleoside Reverse Transcriptase Inhibitors
- OAT3/SLC22A8 Substrates
- Organophosphonates
- Organophosphorus Compounds
- P-glycoprotein substrates
- Purines
- Reverse Transcriptase Inhibitors
- Tenofovir and prodrugs
- Chemical TaxonomyProvided by Classyfire
- Description
- This 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.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Imidazopyrimidines
- Sub Class
- Purines and purine derivatives
- Direct Parent
- 6-aminopurines
- Alternative Parents
- Aminopyrimidines and derivatives / N-substituted imidazoles / Imidolactams / Organic phosphonic acids / Heteroaromatic compounds / Azacyclic compounds / Primary amines / Organopnictogen compounds / Organophosphorus compounds / Organooxygen compounds show 2 more
- Substituents
- 6-aminopurine / Amine / Aminopyrimidine / Aromatic heteropolycyclic compound / Azacycle / Azole / Heteroaromatic compound / Hydrocarbon derivative / Imidazole / Imidolactam show 12 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- phosphonic acids (CHEBI:63625)
- Affected organisms
- Herpes simplex virus
- Hepatitis B virus
- HIV-1
Chemical Identifiers
- UNII
- W4HFE001U5
- CAS number
- 147127-20-6
- InChI Key
- SGOIRFVFHAKUTI-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[C@H](CN1C=NC2=C1N=CN=C2N)OCP(O)(O)=O
References
- General References
- Aloy B, Tazi I, Bagnis CI, Gauthier M, Janus N, Launay-Vacher V, Deray G, Tourret J: Is Tenofovir Alafenamide Safer than Tenofovir Disoproxil Fumarate for the Kidneys? AIDS Rev. 2016 Oct-Dec;18(4):184-192. [Article]
- Deeks ED: Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection. Drugs. 2018 Nov;78(17):1817-1828. doi: 10.1007/s40265-018-1010-7. [Article]
- Ray AS, Fordyce MW, Hitchcock MJ: Tenofovir alafenamide: A novel prodrug of tenofovir for the treatment of Human Immunodeficiency Virus. Antiviral Res. 2016 Jan;125:63-70. doi: 10.1016/j.antiviral.2015.11.009. Epub 2015 Nov 27. [Article]
- Margolis AM, Heverling H, Pham PA, Stolbach A: A review of the toxicity of HIV medications. J Med Toxicol. 2014 Mar;10(1):26-39. doi: 10.1007/s13181-013-0325-8. [Article]
- McConville C, Boyd P, Major I: Efficacy of Tenofovir 1% Vaginal Gel in Reducing the Risk of HIV-1 and HSV-2 Infection. Clin Med Insights Womens Health. 2014 Feb 13;7:1-8. doi: 10.4137/CMWH.S10353. eCollection 2014. [Article]
- Ridruejo E: Treatment of chronic hepatitis B in clinical practice with entecavir or tenofovir. World J Gastroenterol. 2014 Jun 21;20(23):7169-80. doi: 10.3748/wjg.v20.i23.7169. [Article]
- 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. [Article]
- Delaney WE 4th, Ray AS, Yang H, Qi X, Xiong S, Zhu Y, Miller MD: Intracellular metabolism and in vitro activity of tenofovir against hepatitis B virus. Antimicrob Agents Chemother. 2006 Jul;50(7):2471-7. doi: 10.1128/AAC.00138-06. [Article]
- Kearney BP, Yale K, Shah J, Zhong L, Flaherty JF: Pharmacokinetics and dosing recommendations of tenofovir disoproxil fumarate in hepatic or renal impairment. Clin Pharmacokinet. 2006;45(11):1115-24. doi: 10.2165/00003088-200645110-00005. [Article]
- Izzedine H, Launay-Vacher V, Jullien V, Aymard G, Duvivier C, Deray G: Pharmacokinetics of tenofovir in haemodialysis. Nephrol Dial Transplant. 2003 Sep;18(9):1931-3. doi: 10.1093/ndt/gfg327. [Article]
- Sivapalasingam S., Steigbigel N. (2015). Mandell, Douglas and Bennett's Principles and practice of infectious diseases (8th ed.). Elsevier.
- Pubmed books [Link]
- FDA Approved Drug Products: Bictegravir, Emtricitabine, and Tenofovir Alafenamide Oral Tablets [Link]
- FDA Approved Drug Products: VIREAD (tenofovir disoproxil fumarate), for oral use [Link]
- INVIMA: Emtricitabine and Tenofovir Oral Tablet [Link]
- External Links
- Human Metabolome Database
- HMDB0014445
- ChemSpider
- 408154
- BindingDB
- 50450813
- 117466
- ChEBI
- 63625
- ChEMBL
- CHEMBL483
- ZINC
- ZINC000001543475
- PharmGKB
- PA10204
- PDBe Ligand
- TFO
- Wikipedia
- Tenofovir_disoproxil
- PDB Entries
- 1t03 / 8bvs
- MSDS
- Download (79.7 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Not Available Human Immunodeficiency Virus Type 1 (HIV-1) Infection 1 somestatus stop reason just information to hide Not Available Active Not Recruiting Treatment Chronic Hepatitis B Infection 1 somestatus stop reason just information to hide Not Available Approved for Marketing Not Available Chronic Hepatitis B Infection 1 somestatus stop reason just information to hide Not Available Completed Not Available Acquired Immune Deficiency Syndrome (AIDS) 1 somestatus stop reason just information to hide Not Available Completed Not Available Coronavirus Disease 2019 (COVID‑19) / Human Immunodeficiency Virus (HIV) Infections 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, film coated Oral - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 279 ºC 'ChemicalBook' boiling point (°C) 616 ºC at 760 mmHg 'MSDS' water solubility 13.4 mg/ml 'ChemicalBook' logP -1.6 Lastours V. et al. 2011. Antimicrob Agents Chemother. pKa 3.8 and 6.7 Zhang T. et al. 2012. Eur J Pharm Biopharm. - Predicted Properties
Property Value Source Water Solubility 1.87 mg/mL ALOGPS logP -1.5 ALOGPS logP -3.4 Chemaxon logS -2.2 ALOGPS pKa (Strongest Acidic) 1.35 Chemaxon pKa (Strongest Basic) 3.74 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 8 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 136.38 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 67.54 m3·mol-1 Chemaxon Polarizability 25.54 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 166.1954645 predictedDarkChem Lite v0.1.0 [M-H]- 165.3513645 predictedDarkChem Lite v0.1.0 [M-H]- 149.29541 predictedDeepCCS 1.0 (2019) [M-H]- 166.1954645 predictedDarkChem Lite v0.1.0 [M-H]- 165.3513645 predictedDarkChem Lite v0.1.0 [M-H]- 149.29541 predictedDeepCCS 1.0 (2019) [M+H]+ 166.0326645 predictedDarkChem Lite v0.1.0 [M+H]+ 164.1548645 predictedDarkChem Lite v0.1.0 [M+H]+ 151.69096 predictedDeepCCS 1.0 (2019) [M+H]+ 166.0326645 predictedDarkChem Lite v0.1.0 [M+H]+ 164.1548645 predictedDarkChem Lite v0.1.0 [M+H]+ 151.69096 predictedDeepCCS 1.0 (2019) [M+Na]+ 165.9300645 predictedDarkChem Lite v0.1.0 [M+Na]+ 157.69391 predictedDeepCCS 1.0 (2019) [M+Na]+ 165.9300645 predictedDarkChem Lite v0.1.0 [M+Na]+ 157.69391 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Human immunodeficiency virus 1
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Not Available
- Specific Function
- aspartic-type endopeptidase activity
- Gene Name
- pol
- Uniprot ID
- Q72547
- Uniprot Name
- Reverse transcriptase/RNaseH
- Molecular Weight
- 65223.615 Da
References
- McConville C, Boyd P, Major I: Efficacy of Tenofovir 1% Vaginal Gel in Reducing the Risk of HIV-1 and HSV-2 Infection. Clin Med Insights Womens Health. 2014 Feb 13;7:1-8. doi: 10.4137/CMWH.S10353. eCollection 2014. [Article]
- Ray AS, Fordyce MW, Hitchcock MJ: Tenofovir alafenamide: A novel prodrug of tenofovir for the treatment of Human Immunodeficiency Virus. Antiviral Res. 2016 Jan;125:63-70. doi: 10.1016/j.antiviral.2015.11.009. Epub 2015 Nov 27. [Article]
- Cost M, Dezzutti CS, Clark MR, Friend DR, Akil A, Rohan LC: Characterization of UC781-tenofovir combination gel products for HIV-1 infection prevention in an ex vivo ectocervical model. Antimicrob Agents Chemother. 2012 Jun;56(6):3058-66. doi: 10.1128/AAC.06284-11. Epub 2012 Mar 19. [Article]
- Kind
- Protein
- Organism
- Not Available
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Gag-Pol polyprotein Mediates, with Gag polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). Gag-Pol polyprotein may regulate its own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, the polyprotein would promote translation, whereas at high concentration, the polyprotein would encapsidate genomic RNA and then shut off translation.
- Specific Function
- aspartic-type endopeptidase activity
- Gene Name
- gag-pol
- Uniprot ID
- P03366
- Uniprot Name
- Gag-Pol polyprotein
- Molecular Weight
- 163287.51 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- HBV
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Not Available
- Specific Function
- RNA-directed DNA polymerase activity
- Gene Name
- rt
- Uniprot ID
- Q3MS49
- Uniprot Name
- Reverse transcriptase
- Molecular Weight
- 4735.565 Da
References
- Ray AS, Fordyce MW, Hitchcock MJ: Tenofovir alafenamide: A novel prodrug of tenofovir for the treatment of Human Immunodeficiency Virus. Antiviral Res. 2016 Jan;125:63-70. doi: 10.1016/j.antiviral.2015.11.009. Epub 2015 Nov 27. [Article]
- McConville C, Boyd P, Major I: Efficacy of Tenofovir 1% Vaginal Gel in Reducing the Risk of HIV-1 and HSV-2 Infection. Clin Med Insights Womens Health. 2014 Feb 13;7:1-8. doi: 10.4137/CMWH.S10353. eCollection 2014. [Article]
- Friend DR: Pharmaceutical development of microbicide drug products. Pharm Dev Technol. 2010 Dec;15(6):562-81. doi: 10.3109/10837450903369879. Epub 2009 Dec 17. [Article]
- Kind
- Protein
- Organism
- Human herpesvirus 2 (strain 186)
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Replicates viral genomic DNA. The replication complex is composed of six viral proteins: the DNA polymerase, processivity factor, primase, primase-associated factor, helicase, and ssDNA-binding protein. Additionally, the polymerase contains an intrinsic ribonuclease H (RNase H) activity that specifically degrades RNA/DNA heteroduplexes or duplex DNA substrates in the 5' to 3' direction. Therefore, it can catalyze the excision of the RNA primers that initiate the synthesis of Okazaki fragments at a replication fork during viral DNA replication.
- Specific Function
- 3'-5'-DNA exonuclease activity
- Gene Name
- Not Available
- Uniprot ID
- I6TLU5
- Uniprot Name
- DNA polymerase
- Molecular Weight
- 137296.405 Da
References
- McConville C, Boyd P, Major I: Efficacy of Tenofovir 1% Vaginal Gel in Reducing the Risk of HIV-1 and HSV-2 Infection. Clin Med Insights Womens Health. 2014 Feb 13;7:1-8. doi: 10.4137/CMWH.S10353. eCollection 2014. [Article]
- Ray AS, Fordyce MW, Hitchcock MJ: Tenofovir alafenamide: A novel prodrug of tenofovir for the treatment of Human Immunodeficiency Virus. Antiviral Res. 2016 Jan;125:63-70. doi: 10.1016/j.antiviral.2015.11.009. Epub 2015 Nov 27. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General 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. Involved in cell proliferation, differentiation and development, signal transduction, G protein-coupled receptor endocytosis, and gene expression. Required for neural development including neural patterning and cell fate determination. During GZMA-mediated cell death, works in concert with TREX1. NME1 nicks one strand of DNA and TREX1 removes bases from the free 3' end to enhance DNA damage and prevent DNA end reannealing and rapid repair
- Specific Function
- 3'-5' exonuclease activity
- Gene Name
- NME1
- Uniprot ID
- P15531
- Uniprot Name
- Nucleoside diphosphate kinase A
- Molecular Weight
- 17148.635 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General 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 (By similarity). Negatively regulates Rho activity by interacting with AKAP13/LBC (PubMed:15249197). Acts as a transcriptional activator of the MYC gene; binds DNA non-specifically (PubMed:19435876, PubMed:8392752). Binds to both single-stranded guanine- and cytosine-rich strands within the nuclease hypersensitive element (NHE) III(1) region of the MYC gene promoter. Does not bind to duplex NHE III(1) (PubMed:19435876). Has G-quadruplex (G4) DNA-binding activity, which is independent of its nucleotide-binding and kinase activity. Binds both folded and unfolded G4 with similar low nanomolar affinities. Stabilizes folded G4s regardless of whether they are prefolded or not (PubMed:25679041). Exhibits histidine protein kinase activity (PubMed:20946858)
- Specific Function
- ATP binding
- Gene Name
- NME2
- Uniprot ID
- P22392
- Uniprot Name
- Nucleoside diphosphate kinase B
- Molecular Weight
- 17297.935 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP. Also displays broad nucleoside diphosphate kinase activity. Plays an important role in cellular energy homeostasis and in adenine nucleotide metabolism (By similarity) (PubMed:21080915, PubMed:23416111, PubMed:2542324). Also catalyzes at a very low rate the synthesis of thiamine triphosphate (ThTP) from thiamine diphosphate (ThDP) and ADP (By similarity)
- Specific Function
- adenylate kinase activity
- Gene Name
- AK1
- Uniprot ID
- P00568
- Uniprot Name
- Adenylate kinase isoenzyme 1
- Molecular Weight
- 21634.725 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General 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
- Specific Function
- adenylate kinase activity
- Gene Name
- AK2
- Uniprot ID
- P54819
- Uniprot Name
- Adenylate kinase 2, mitochondrial
- Molecular Weight
- 26477.44 Da
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Binder
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- Deeks ED: Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection. Drugs. 2018 Nov;78(17):1817-1828. doi: 10.1007/s40265-018-1010-7. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- Murakami E, Wang T, Park Y, Hao J, Lepist EI, Babusis D, Ray AS: Implications of efficient hepatic delivery by tenofovir alafenamide (GS-7340) for hepatitis B virus therapy. Antimicrob Agents Chemother. 2015;59(6):3563-9. doi: 10.1128/AAC.00128-15. Epub 2015 Apr 13. [Article]
- Droste JA, Verweij-van Wissen CP, Kearney BP, Buffels R, Vanhorssen PJ, Hekster YA, Burger DM: Pharmacokinetic study of tenofovir disoproxil fumarate combined with rifampin in healthy volunteers. Antimicrob Agents Chemother. 2005 Feb;49(2):680-4. doi: 10.1128/AAC.49.2.680-684.2005. [Article]
- Begley R, Das M, Zhong L, Ling J, Kearney BP, Custodio JM: Pharmacokinetics of Tenofovir Alafenamide When Coadministered With Other HIV Antiretrovirals. J Acquir Immune Defic Syndr. 2018 Aug 1;78(4):465-472. doi: 10.1097/QAI.0000000000001699. [Article]
- Custodio JM, Fordyce M, Garner W, Vimal M, Ling KH, Kearney BP, Ramanathan S: Pharmacokinetics and Safety of Tenofovir Alafenamide in HIV-Uninfected Subjects with Severe Renal Impairment. Antimicrob Agents Chemother. 2016 Aug 22;60(9):5135-40. doi: 10.1128/AAC.00005-16. Print 2016 Sep. [Article]
- Moss DM, Domanico P, Watkins M, Park S, Randolph R, Wring S, Rajoli RKR, Hobson J, Rannard S, Siccardi M, Owen A: Simulating Intestinal Transporter and Enzyme Activity in a Physiologically Based Pharmacokinetic Model for Tenofovir Disoproxil Fumarate. Antimicrob Agents Chemother. 2017 Jun 27;61(7). pii: AAC.00105-17. doi: 10.1128/AAC.00105-17. Print 2017 Jul. [Article]
- Soriano V, Labarga P, Fernandez-Montero JV, Mendoza C, Benitez-Gutierrez L, Pena JM, Barreiro P: Drug interactions in HIV-infected patients treated for hepatitis C. Expert Opin Drug Metab Toxicol. 2017 Aug;13(8):807-816. doi: 10.1080/17425255.2017.1351942. Epub 2017 Jul 13. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as 2-oxoglutarate or glutarate (PubMed:11669456, PubMed:11907186, PubMed:14675047, PubMed:22108572, PubMed:23832370, PubMed:28534121, PubMed:9950961). Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine (PubMed:9887087). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion (PubMed:11907186). Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP (PubMed:26377792). Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain (PubMed:22108572, PubMed:23832370). May transport glutamate (PubMed:26377792). Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body (PubMed:11669456, PubMed:14675047). Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate (PubMed:14675047, PubMed:26377792). Xenobiotics include the mycotoxin ochratoxin (OTA) (PubMed:11669456). May also contribute to the transport of organic compounds in testes across the blood-testis-barrier (PubMed:35307651)
- Specific Function
- alpha-ketoglutarate transmembrane transporter activity
- Gene Name
- SLC22A6
- Uniprot ID
- Q4U2R8
- Uniprot Name
- Solute carrier family 22 member 6
- Molecular Weight
- 61815.78 Da
References
- Aloy B, Tazi I, Bagnis CI, Gauthier M, Janus N, Launay-Vacher V, Deray G, Tourret J: Is Tenofovir Alafenamide Safer than Tenofovir Disoproxil Fumarate for the Kidneys? AIDS Rev. 2016 Oct-Dec;18(4):184-192. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient (PubMed:14586168, PubMed:15644426, PubMed:15846473, PubMed:16455804, PubMed:31553721). Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) (PubMed:14586168, PubMed:15846473, PubMed:15864504, PubMed:22108572, PubMed:23832370). Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain (PubMed:11306713, PubMed:14586168, PubMed:15846473). E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange (PubMed:26377792). Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule (PubMed:11907186). Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate (PubMed:22108572, PubMed:23832370). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside (PubMed:15644426). May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate (PubMed:11669456, PubMed:15846473, PubMed:16455804). Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) (PubMed:14675047). May contribute to the release of cortisol in the adrenals (PubMed:15864504). Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (By similarity). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB). In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
- Specific Function
- organic anion transmembrane transporter activity
- Gene Name
- SLC22A8
- Uniprot ID
- Q8TCC7
- Uniprot Name
- Organic anion transporter 3
- Molecular Weight
- 59855.585 Da
References
- Aloy B, Tazi I, Bagnis CI, Gauthier M, Janus N, Launay-Vacher V, Deray G, Tourret J: Is Tenofovir Alafenamide Safer than Tenofovir Disoproxil Fumarate for the Kidneys? AIDS Rev. 2016 Oct-Dec;18(4):184-192. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells. Transports a range of endogenous molecules that have a key role in cellular communication and signaling, including cyclic nucleotides such as cyclic AMP (cAMP) and cyclic GMP (cGMP), bile acids, steroid conjugates, urate, and prostaglandins (PubMed:11856762, PubMed:12523936, PubMed:12835412, PubMed:12883481, PubMed:15364914, PubMed:15454390, PubMed:16282361, PubMed:17959747, PubMed:18300232, PubMed:26721430). Mediates the ATP-dependent efflux of glutathione conjugates such as leukotriene C4 (LTC4) and leukotriene B4 (LTB4) too. The presence of GSH is necessary for the ATP-dependent transport of LTB4, whereas GSH is not required for the transport of LTC4 (PubMed:17959747). Mediates the cotransport of bile acids with reduced glutathione (GSH) (PubMed:12523936, PubMed:12883481, PubMed:16282361). Transports a wide range of drugs and their metabolites, including anticancer, antiviral and antibiotics molecules (PubMed:11856762, PubMed:12105214, PubMed:15454390, PubMed:17344354, PubMed:18300232). Confers resistance to anticancer agents such as methotrexate (PubMed:11106685)
- Specific Function
- 15-hydroxyprostaglandin dehydrogenase (NAD+) activity
- Gene Name
- ABCC4
- Uniprot ID
- O15439
- Uniprot Name
- ATP-binding cassette sub-family C member 4
- Molecular Weight
- 149525.33 Da
References
- Aloy B, Tazi I, Bagnis CI, Gauthier M, Janus N, Launay-Vacher V, Deray G, Tourret J: Is Tenofovir Alafenamide Safer than Tenofovir Disoproxil Fumarate for the Kidneys? AIDS Rev. 2016 Oct-Dec;18(4):184-192. [Article]
Drug created at June 24, 2018 16:23 / Updated at August 26, 2024 19:23