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Overview
- Description
- A medication used to treat herpes infections in the eye as well as a certain viral infection in some patients with weakened immune systems.
- Description
- A medication used to treat herpes infections in the eye as well as a certain viral infection in some patients with weakened immune systems.
- DrugBank ID
- DB01004
- Type
- Small Molecule
- Clinical Trials
- Phase 0
- 1
- Phase 1
- 22
- Phase 2
- 25
- Phase 3
- 19
- Phase 4
- 12
- Mechanism of Action
- DNA polymerase catalytic subunit (HHV-1)Inhibitor
- DNAIncorporation into and destabilization
- Thymidine kinase (HHV-1)Substrate
- DNA polymerase catalytic subunit (HHV-1)
Identification
- Summary
Ganciclovir is a DNA polymerase inhibitor used to treat cytomegalovirus and herpetic keratitis of the eye.
- Brand Names
- Cytovene, Zirgan
- Generic Name
- Ganciclovir
- DrugBank Accession Number
- DB01004
- Background
An acyclovir analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 255.2306
Monoisotopic: 255.096753929 - Chemical Formula
- C9H13N5O4
- Synonyms
- 2-(6-Amino-purin-9-ylmethoxy)-propane-1,3-diol
- 2-amino-9-((1,3-dihydroxypropan-2-yloxy)methyl)-1H-purin-6(9H)-one
- 2-amino-9-((1,3-dihydroxypropan-2-yloxy)methyl)-3H-purin-6(9H)-one
- 2-amino-9-((1,3-dihydroxypropan-2-yloxy)methyl)-9H-purin-6-ol
- 2-Amino-9-(2-hydroxy-1-hydroxymethyl-ethoxymethyl)-1,9-dihydro-purin-6-one
- 2-amino-9-(2-hydroxy-1-hydroxymethylethoxymethyl)-6,9-dihydro-1H-6-purinone
- 9-((2-Hydroxy-1-(hydroxymethyl)ethoxy)methyl)guanine
- 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine
- GA2
- Ganciclovir
- Ganciclovirum
- Gancyclovir
- External IDs
- BW 759U
- BW-759U
- RS-21592
Pharmacology
- Indication
For induction and maintenance in the treatment of cytomegalovirus (CMV) retinitis in immunocompromised patients, including patients with acquired immunodeficiency syndrome (AIDS). Also used in the treatment of severe cytomegalovirus (CMV) disease, including CMV pneumonia, CMV gastrointestinal disease, and disseminated CMV infections, in immunocompromised patients.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Prophylaxis of Cmv infection •••••••••••• Prophylaxis of Cmv infection ••• ••••• Treatment of Cmv colitis ••• ••••• Treatment of Cmv esophagitis ••• ••••• Treatment of Cmv neurological disease ••• ••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Learn moreAvoid life-threatening adverse drug events with our Clinical APILearn more- Pharmacodynamics
Ganciclovir is a synthetic nucleoside analogue of 2'-deoxyguanosine that inhibits replication of herpes viruses bothin vitro andin vivo. Sensitive human viruses include cytomegalovirus (CMV), herpes simplex virus -1 and -2 (HSV-1, HSV-2), Epstein-Barr virus (EBV) and varicella zoster virus (VZV), however clinical studies have been limited to assessment of efficacy in patients with CMV infection. Ganciclovir is a prodrug that is structurally similar to acyclovir. It inhibits virus replication by its encorporation into viral DNA. This encorporation inhibits dATP and leads to defective DNA, ceasing or retarding the viral machinery required to spread the virus to other cells.
- Mechanism of action
Ganciclovir's antiviral activity inhibits virus replication. This inhibitory action is highly selective as the drug must be converted to the active form by a virus-encoded cellular enzyme, thymidine kinase (TK). TK catalyzes phosphorylation of ganciclovir to the monophosphate, which is then subsequently converted into the diphosphate by cellular guanylate kinase and into the triphosphate by a number of cellular enzymes.In vitro, ganciclovir triphosphate stops replication of herpes viral DNA. When used as a substrate for viral DNA polymerase, ganciclovir triphosphate competitively inhibits dATP leading to the formation of 'faulty' DNA. This is where ganciclovir triphosphate is incorporated into the DNA strand replacing many of the adenosine bases. This results in the prevention of DNA synthesis, as phosphodiester bridges can longer to be built, destabilizing the strand. Ganciclovir inhibits viral DNA polymerases more effectively than it does cellular polymerase, and chain elongation resumes when ganciclovir is removed.
Target Actions Organism ADNA polymerase catalytic subunit inhibitorHHV-1 ADNA incorporation into and destabilizationHumans AThymidine kinase substrateHHV-1 - Absorption
Poorly absorbed systemically following oral administration. Bioavailability under fasting conditions is approximately 5%, and when administered with food, 6 to 9% (about 30% with a fatty meal).
- Volume of distribution
- 0.74 ± 0.15 L/kg
- Protein binding
1 to 2%
- Metabolism
Little to no metabolism, about 90% of plasma ganciclovir is eliminated unchanged in the urine.
- Route of elimination
Renal excretion of unchanged drug by glomerular filtration and active tubular secretion is the major route of elimination of ganciclovir.
- Half-life
2.5 to 3.6 hours (mean 2.9 hours) when administered intravenously in adults. 3.1 to 5.5 hours when administered orally in adults. Renal function impairment causes a marked increase in half life (9 to 30 hours intravenously, 15.7 to 18.2 hours orally).
- Clearance
- 128 +/- 63 mL/min [Patients with Renal Impairment (Clcr=50-79 mL/min)]
- 57+/- 8 mL/min [Patients with Renal Impairment (Clcr=25-49 mL/min)]
- 30 +/- 13 mL/min [Patients with Renal Impairment (Clcr<25 mL/min)]
- 4.7+/- 2.2 mL/min/kg [pediatric patients, aged 9 months to 12 years]
- 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!See the dataImprove decision support & research outcomes with our structured adverse effects data.See a data sample- Toxicity
Oral, mouse LD50: > 2g/kg. Intravenous, dog LD50: > 150mg/kg. Symptoms of overdose include irreversible pancytopenia, worsening GI symptoms, and acute renal failure. Suspected cancer agent.
- 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 The risk or severity of cytopenia can be increased when Ganciclovir is combined with Abacavir. Abemaciclib The excretion of Abemaciclib can be decreased when combined with Ganciclovir. Acamprosate The excretion of Acamprosate can be decreased when combined with Ganciclovir. Aceclofenac Aceclofenac may decrease the excretion rate of Ganciclovir which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Ganciclovir which could result in a higher serum level. - Food Interactions
- Take with food. Food increases bioavailability.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access nowAccess drug product information from over 10 global regions.Access now- Product Ingredients
Ingredient UNII CAS InChI Key Ganciclovir sodium 02L083W284 107910-75-8 JJICLMJFIKGAAU-UHFFFAOYSA-M - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Cytovene Powder, for solution 500 mg / vial Intravenous Cheplapharm Arzneimittel Gmbh 1995-12-31 Not applicable Canada 
Cytovene - Cap 250mg Capsule 250 mg / cap Oral Hoffmann La Roche 1995-12-31 2007-08-02 Canada Cytovene Inj 500mg/vial Powder, for solution 500 mg / vial Intravenous Syntex Inc. 1990-12-31 1996-09-30 Canada Cytovene IV Injection, powder, lyophilized, for solution 500 mg/10mL Intravenous H2-Pharma, LLC 1989-06-23 Not applicable US 
Cytovene IV Injection, powder, lyophilized, for solution 500 mg/10mL Intravenous Genentech, Inc. 1989-06-23 2020-01-31 US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ganciclovir Injection, powder, lyophilized, for solution 500 mg/10mL Intravenous Leucadia Pharmaceuticals 2019-06-20 2019-06-20 US Ganciclovir Injection, solution 500 mg/10mL Intravenous Pharmascience Inc 2018-04-24 Not applicable US Ganciclovir Injection, powder, lyophilized, for solution 500 mg/10mL Intravenous ENDO USA, Inc. 2016-12-06 Not applicable US Ganciclovir Capsule 250 mg/1 Oral Ranbaxy Italia S.P.A. 2003-08-27 Not applicable US Ganciclovir Injection, solution 50 mg/1mL Intravenous Sagent Pharmaceuticals 2018-02-15 Not applicable US
Categories
- ATC Codes
- J05AB06 — Ganciclovir
- J05AB — Nucleosides and nucleotides excl. reverse transcriptase inhibitors
- J05A — DIRECT ACTING ANTIVIRALS
- J05 — ANTIVIRALS FOR SYSTEMIC USE
- J — ANTIINFECTIVES FOR SYSTEMIC USE
- Drug Categories
- Agents Causing Muscle Toxicity
- Agents that reduce seizure threshold
- Anti-Infective Agents
- Antiinfectives for Systemic Use
- Antiviral Agents
- Antivirals for Systemic Use
- Cytomegalovirus Nucleoside Analog DNA Polymerase Inhibitor
- Direct Acting Antivirals
- Drugs that are Mainly Renally Excreted
- Ganciclovir and prodrug
- Heterocyclic Compounds, Fused-Ring
- MATE 1 Substrates
- MATE 2 Substrates
- MATE substrates
- Nucleic Acid Synthesis Inhibitors
- Nucleoside Analog Antiviral
- Nucleosides and Nucleotides
- Nucleosides and Nucleotides Excl. Reverse Transcriptase Inhibitors
- OAT1/SLC22A6 inhibitors
- OAT3/SLC22A8 Inhibitors
- OCT1 inhibitors
- OCT1 substrates
- Ophthalmologicals
- Purines
- Purinones
- Sensory Organs
- Chemical TaxonomyProvided byClassyfire
- Description
- This compound belongs to the class of organic compounds known as hypoxanthines. These are compounds containing the purine derivative 1H-purin-6(9H)-one. 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
- Hypoxanthines
- Alternative Parents
- 6-oxopurines /Pyrimidones /Glycerolipids /Aminopyrimidines and derivatives /N-substituted imidazoles /Vinylogous amides /Heteroaromatic compounds /Azacyclic compounds /Primary amines /Primary alcohols /Organopnictogen compounds /Organic oxides /Hydrocarbon derivatives show 3 more
- Substituents
- 6-oxopurine /Alcohol /Amine /Aminopyrimidine /Aromatic heteropolycyclic compound /Azacycle /Azole /Glycerolipid /Heteroaromatic compound /Hydrocarbon derivative /Hypoxanthine /Imidazole /N-substituted imidazole /Organic nitrogen compound /Organic oxide /Organic oxygen compound /Organonitrogen compound /Organooxygen compound /Organopnictogen compound /Primary alcohol /Primary amine /Pyrimidine /Pyrimidone /Vinylogous amide show 14 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- oxopurine, 2-aminopurines (CHEBI:465284)
- Affected organisms
- Human Herpes Virus
Chemical Identifiers
- UNII
- P9G3CKZ4P5
- CAS number
- 82410-32-0
- InChI Key
- IRSCQMHQWWYFCW-UHFFFAOYSA-N
- InChI
- InChI=1S/C9H13N5O4/c10-9-12-7-6(8(17)13-9)11-3-14(7)4-18-5(1-15)2-16/h3,5,15-16H,1-2,4H2,(H3,10,12,13,17)
- IUPAC Name
- 2-amino-9-{[(1,3-dihydroxypropan-2-yl)oxy]methyl}-6,9-dihydro-1H-purin-6-one
- SMILES
- NC1=NC2=C(N=CN2COC(CO)CO)C(=O)N1
References
- Synthesis Reference
- US4355032
- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0015139
- KEGG Drug
- D00333
- PubChem Compound
- 3454
- PubChem Substance
- 46507294
- ChemSpider
- 3336
- BindingDB
- 85707
- RxNav
- 4678
- ChEBI
- 465284
- ChEMBL
- CHEMBL182
- ZINC
- ZINC000000001505
- Therapeutic Targets Database
- DAP000645
- PharmGKB
- PA449733
- PDBe Ligand
- GA2
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Ganciclovir
- PDB Entries
- 1ki2 /4da6
- FDA label
- Download(489 KB)
- MSDS
- Download(119 KB)
Clinical Trials
- Clinical Trials
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Pharmacoeconomics
- Manufacturers
- Roche palo alto llc
- Ranbaxy laboratories ltd
- Bausch and lomb inc
- App pharmaceuticals llc
- Bedford laboratories div ben venue laboratories inc
- Packagers
- Alliance Medical Products
- APP Pharmaceuticals
- Bausch & Lomb Inc.
- Bedford Labs
- F Hoffmann La Roche Ltd.
- F Hoffmann-La Roche Ltd.
- JHP Pharmaceuticals LLC
- Physicians Total Care Inc.
- Ranbaxy Laboratories
- Sirion Therapeutics
- Dosage Forms
Form Route Strength Solution Intravenous 543.080 mg Solution Intravenous 500.000 mg Capsule Oral 250 MG Injection, powder, for solution Parenteral 500 MG Capsule Oral Injection, powder, for solution 543 mg Powder Capsule, liquid filled Oral 250 mg Injection, powder, for solution Intravenous 500 mg Injection, powder, lyophilized, for solution Intravenous 500 mg Capsule Oral 250 mg / cap Powder, for solution Intravenous 500 mg / vial Capsule Oral 500 mg / cap Gel Ophthalmic 0.15 % w/w Capsule Oral 250 mg/1 Capsule Oral 500 mg/1 Injection, powder, lyophilized, for solution Intravenous 50 mg/1mL Injection, powder, lyophilized, for solution Intravenous 500 mg/10mL Injection, powder, lyophilized, for solution Intraventricular 50 mg/1mL Injection, solution Intravenous 2 mg/1mL Injection, solution Intravenous 50 mg/1mL Injection, solution Intravenous 500 mg/10mL Injection, powder, for solution 500 MG Powder, for solution Intravenous Injection, solution, concentrate Intravenous 500 mg/1vial Solution, gel forming / drops Conjunctival 150 mg Powder 500 mg Injection, solution, concentrate Intravenous 500 mg Injection, solution, concentrate Intravenous 50 mg Solution Intravenous 543.10 mg Injection, solution Intravenous 500 mg Injection Intravenous 500 mg Solution Intravenous 543.000 mg Solution Parenteral 500.000 mg Gel Ophthalmic Gel Ophthalmic 1.5 MG/G Ointment Ophthalmic 0.15 g/100g Solution, gel forming / drops Ophthalmic 0.15 g Gel Ophthalmic 1.500 mg Implant Intravitreal 4.5 mg/1 Implant Intravitreal 4.5 mg / imp Gel Ophthalmic 1.5 mg/1g Injection, powder, lyophilized, for solution 500 mg/1vial Injection, powder, lyophilized, for solution Intravenous 500 mg/1vial - Prices
Unit description Cost Unit Vitrasert 4.5 mg implant 19200.0USD implant Cytovene 500 mg vial 81.06USD vial Cytovene 500 mg/vial 46.41USD vial Zirgan 0.15% ophthalmic gel 33.6USD g Ganciclovir 500 mg capsule 19.66USD capsule Cytovene 500 mg capsule 10.99USD capsule Cytovene 250 mg capsule 5.61USD capsule Ganciclovir 250 mg capsule 4.72USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5378475 No 1995-01-03 2012-01-03 US US9486530 No 2016-11-08 2034-09-02 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 250 dec °C PhysProp water solubility 4300 mg/L (at 25 °C) MERCK INDEX (1996); pH 7 logP -1.66 SANGSTER (1993) Caco2 permeability -6.27 ADME Research, USCD - Predicted Properties
Property Value Source Water Solubility 11.5 mg/mL ALOGPS logP -1.8 ALOGPS logP -2.2 Chemaxon logS -1.4 ALOGPS pKa (Strongest Acidic) 10.16 Chemaxon pKa (Strongest Basic) 0.58 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 134.99 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 61.03 m3·mol-1 Chemaxon Polarizability 24.15 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
Property Value Probability Human Intestinal Absorption + 0.9443 Blood Brain Barrier + 0.9866 Caco-2 permeable - 0.8957 P-glycoprotein substrate Substrate 0.5767 P-glycoprotein inhibitor I Non-inhibitor 0.932 P-glycoprotein inhibitor II Non-inhibitor 0.8381 Renal organic cation transporter Non-inhibitor 0.8459 CYP450 2C9 substrate Non-substrate 0.8907 CYP450 2D6 substrate Non-substrate 0.8225 CYP450 3A4 substrate Non-substrate 0.5919 CYP450 1A2 substrate Non-inhibitor 0.9045 CYP450 2C9 inhibitor Non-inhibitor 0.907 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Non-inhibitor 0.96 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.935 Ames test Non AMES toxic 0.6094 Carcinogenicity Non-carcinogens 0.8875 Biodegradation Not ready biodegradable 0.9368 Rat acute toxicity 2.0348 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9611 hERG inhibition (predictor II) Non-inhibitor 0.8943
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 160.101906 predictedDarkChem Lite v0.1.0 [M-H]- 157.643106 predictedDarkChem Lite v0.1.0 [M-H]- 155.05626 predictedDeepCCS 1.0 (2019) [M+H]+ 159.431206 predictedDarkChem Lite v0.1.0 [M+H]+ 157.667306 predictedDarkChem Lite v0.1.0 [M+H]+ 157.41426 predictedDeepCCS 1.0 (2019) [M+Na]+ 160.061206 predictedDarkChem Lite v0.1.0 [M+Na]+ 164.71614 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- HHV-1
- 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
- P04293
- Uniprot Name
- DNA polymerase catalytic subunit
- Molecular Weight
- 136419.66 Da
References
- Boivin G, Goyette N, Gilbert C, Covington E: Analysis of cytomegalovirus DNA polymerase (UL54) mutations in solid organ transplant patients receiving valganciclovir or ganciclovir prophylaxis. J Med Virol. 2005 Nov;77(3):425-9. [Article]
- Wang JT, Yang PW, Lee CP, Han CH, Tsai CH, Chen MR: Detection of Epstein-Barr virus BGLF4 protein kinase in virus replication compartments and virus particles. J Gen Virol. 2005 Dec;86(Pt 12):3215-25. [Article]
- Shi R, Azzi A, Gilbert C, Boivin G, Lin SX: Three-dimensional modeling of cytomegalovirus DNA polymerase and preliminary analysis of drug resistance. Proteins. 2006 Aug 1;64(2):301-7. [Article]
- 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]
Yes
Incorporation into and destabilization
References
- Martin M, Azzi A, Lin SX, Boivin G: Opposite effect of two cytomegalovirus DNA polymerase mutations on replicative capacity and polymerase activity. Antivir Ther. 2010;15(4):579-86. doi: 10.3851/IMP1565. [Article]
- Boivin G, Goyette N, Gilbert C, Covington E: Analysis of cytomegalovirus DNA polymerase (UL54) mutations in solid organ transplant patients receiving valganciclovir or ganciclovir prophylaxis. J Med Virol. 2005 Nov;77(3):425-9. [Article]
- Marfori JE, Exner MM, Marousek GI, Chou S, Drew WL: Development of new cytomegalovirus UL97 and DNA polymerase mutations conferring drug resistance after valganciclovir therapy in allogeneic stem cell recipients. J Clin Virol. 2007 Feb;38(2):120-5. Epub 2006 Dec 8. [Article]
- Potena L, Holweg CT, Chin C, Luikart H, Weisshaar D, Narasimhan B, Fearon WF, Lewis DB, Cooke JP, Mocarski ES, Valantine HA: Acute rejection and cardiac allograft vascular disease is reduced by suppression of subclinical cytomegalovirus infection. Transplantation. 2006 Aug 15;82(3):398-405. [Article]
- Kind
- Protein
- Organism
- HHV-1
- Pharmacological action
- Yes
- Actions
- Substrate
- General Function
- Catalyzes the transfer of the gamma-phospho group of ATP to thymidine to generate dTMP in the salvage pathway of pyrimidine synthesis. The dTMP serves as a substrate for DNA polymerase during viral DNA replication. Allows the virus to be reactivated and to grow in non-proliferative cells lacking a high concentration of phosphorylated nucleic acid precursors.
- Specific Function
- ATP binding
- Gene Name
- TK
- Uniprot ID
- Q9QNF7
- Uniprot Name
- Thymidine kinase
- Molecular Weight
- 40896.475 Da
References
- Champness JN, Bennett MS, Wien F, Visse R, Summers WC, Herdewijn P, de Clerq E, Ostrowski T, Jarvest RL, Sanderson MR: Exploring the active site of herpes simplex virus type-1 thymidine kinase by X-ray crystallography of complexes with aciclovir and other ligands. Proteins. 1998 Aug 15;32(3):350-61. [Article]
- Beck C, Cayeux S, Lupton SD, Dorken B, Blankenstein T: The thymidine kinase/ganciclovir-mediated "suicide" effect is variable in different tumor cells. Hum Gene Ther. 1995 Dec;6(12):1525-30. doi: 10.1089/hum.1995.6.12-1525. [Article]
- Garin MI, Garrett E, Tiberghien P, Apperley JF, Chalmers D, Melo JV, Ferrand C: Molecular mechanism for ganciclovir resistance in human T lymphocytes transduced with retroviral vectors carrying the herpes simplex virus thymidine kinase gene. Blood. 2001 Jan 1;97(1):122-9. doi: 10.1182/blood.v97.1.122. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:11388889, PubMed:11408531, PubMed:12439218, PubMed:12719534, PubMed:15389554, PubMed:16263091, PubMed:16272756, PubMed:16581093, PubMed:19536068, PubMed:21128598, PubMed:23680637, PubMed:24961373, PubMed:34040533, PubMed:9187257, PubMed:9260930, PubMed:9655880). Functions as a pH- and Na(+)-independent, bidirectional transporter (By similarity). Cation cellular uptake or release is driven by the electrochemical potential (i.e. membrane potential and concentration gradient) and substrate selectivity (By similarity). Hydrophobicity is a major requirement for recognition in polyvalent substrates and inhibitors (By similarity). Primarily expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (By similarity). Most likely functions as an uptake carrier in enterocytes contributing to the intestinal elimination of organic cations from the systemic circulation (PubMed:16263091). Transports endogenous monoamines such as N-1-methylnicotinamide (NMN), guanidine, histamine, neurotransmitters dopamine, serotonin and adrenaline (PubMed:12439218, PubMed:24961373, PubMed:35469921, PubMed:9260930). Also transports natural polyamines such as spermidine, agmatine and putrescine at low affinity, but relatively high turnover (PubMed:21128598). Involved in the hepatic uptake of vitamin B1/thiamine, hence regulating hepatic lipid and energy metabolism (PubMed:24961373). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with lower efficency (PubMed:17460754). Also capable of transporting non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). May contribute to the transport of cationic compounds in testes across the blood-testis-barrier (Probable). Also involved in the uptake of xenobiotics tributylmethylammonium (TBuMA), quinidine, N-methyl-quinine (NMQ), N-methyl-quinidine (NMQD) N-(4,4-azo-n-pentyl)-quinuclidine (APQ), azidoprocainamide methoiodide (AMP), N-(4,4-azo-n-pentyl)-21-deoxyajmalinium (APDA) and 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:11408531, PubMed:15389554, PubMed:35469921, PubMed:9260930)
- Specific Function
- (R)-carnitine transmembrane transporter activity
- Gene Name
- SLC22A1
- Uniprot ID
- O15245
- Uniprot Name
- Solute carrier family 22 member 1
- Molecular Weight
- 61153.345 Da
References
- Takeda M, Khamdang S, Narikawa S, Kimura H, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Endou H: Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24. [Article]
- Wagner DJ, Hu T, Wang J: Polyspecific organic cation transporters and their impact on drug intracellular levels and pharmacodynamics. Pharmacol Res. 2016 Sep;111:237-246. doi: 10.1016/j.phrs.2016.06.002. Epub 2016 Jun 16. [Article]
- Shugarts S, Benet LZ: The role of transporters in the pharmacokinetics of orally administered drugs. Pharm Res. 2009 Sep;26(9):2039-54. doi: 10.1007/s11095-009-9924-0. Epub 2009 Jun 30. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- 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
- Takeda M, Khamdang S, Narikawa S, Kimura H, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Endou H: Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- 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
- Takeda M, Khamdang S, Narikawa S, Kimura H, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Endou H: Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Functions as a Na(+)-independent bidirectional multispecific transporter (PubMed:11327718, PubMed:18216183, PubMed:21446918, PubMed:28945155). Contributes to the renal and hepatic elimination of endogenous organic compounds from the systemic circulation into the urine and bile, respectively (PubMed:11327718, PubMed:25904762). Capable of transporting a wide range of purine and pyrimidine nucleobases, nucleosides and nucleotides, with cGMP, 2'deoxyguanosine and GMP being the preferred substrates (PubMed:11327718, PubMed:18216183, PubMed:26377792, PubMed:28945155). Functions as a pH- and chloride-independent cGMP bidirectional facilitative transporter that can regulate both intracellular and extracellular levels of cGMP and may be involved in cGMP signaling pathways (PubMed:18216183, PubMed:26377792). Mediates orotate/glutamate bidirectional exchange and most likely display a physiological role in hepatic release of glutamate into the blood (PubMed:21446918). Involved in renal secretion and possible reabsorption of creatinine (PubMed:25904762, PubMed:28945155). Able to uptake prostaglandin E2 (PGE2) and may contribute to PGE2 renal excretion (Probable). Also transports alpha-ketoglutarate and urate (PubMed:11327718, PubMed:26377792). Apart from the orotate/glutamate exchange, the counterions for the uptake of other SLC22A7/OAT2 substrates remain to be identified (PubMed:26377792)
- Specific Function
- alpha-ketoglutarate transmembrane transporter activity
- Gene Name
- SLC22A7
- Uniprot ID
- Q9Y694
- Uniprot Name
- Solute carrier family 22 member 7
- Molecular Weight
- 60025.025 Da
References
- Takeda M, Khamdang S, Narikawa S, Kimura H, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Endou H: Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Multidrug efflux pump that functions as a H(+)/organic cation antiporter (PubMed:16330770, PubMed:17509534). Plays a physiological role in the excretion of cationic compounds including endogenous metabolites, drugs, toxins through the kidney and liver, into urine and bile respectively (PubMed:16330770, PubMed:17495125, PubMed:17509534, PubMed:17582384, PubMed:18305230, PubMed:19158817, PubMed:21128598, PubMed:24961373). Mediates the efflux of endogenous compounds such as creatinine, vitamin B1/thiamine, agmatine and estrone-3-sulfate (PubMed:16330770, PubMed:17495125, PubMed:17509534, PubMed:17582384, PubMed:18305230, PubMed:19158817, PubMed:21128598, PubMed:24961373). May also contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable)
- Specific Function
- antiporter activity
- Gene Name
- SLC47A1
- Uniprot ID
- Q96FL8
- Uniprot Name
- Multidrug and toxin extrusion protein 1
- Molecular Weight
- 61921.585 Da
References
- Tanihara Y, Masuda S, Sato T, Katsura T, Ogawa O, Inui K: Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol. 2007 Jul 15;74(2):359-71. doi: 10.1016/j.bcp.2007.04.010. Epub 2007 Apr 13. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Multidrug efflux pump that functions as a H(+)/organic cation antiporter. Mediates the efflux of cationic compounds, such as the model cations, tetraethylammonium (TEA) and 1-methyl-4-phenylpyridinium (MPP+), the platinum-based drug oxaliplatin or weak bases that are positively charged at physiological pH, cimetidine, the platinum-based drugs cisplatin and oxaliplatin or the antidiabetic drug metformin. Mediates the efflux of endogenous compounds such as, creatinine, thiamine and estrone-3-sulfate. Plays a physiological role in the excretion of drugs, toxins and endogenous metabolites through the kidney
- Specific Function
- antiporter activity
- Gene Name
- SLC47A2
- Uniprot ID
- Q86VL8
- Uniprot Name
- Multidrug and toxin extrusion protein 2
- Molecular Weight
- 65083.915 Da
References
- Tanihara Y, Masuda S, Sato T, Katsura T, Ogawa O, Inui K: Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol. 2007 Jul 15;74(2):359-71. doi: 10.1016/j.bcp.2007.04.010. Epub 2007 Apr 13. [Article]
- Nies AT, Damme K, Schaeffeler E, Schwab M: Multidrug and toxin extrusion proteins as transporters of antimicrobial drugs. Expert Opin Drug Metab Toxicol. 2012 Dec;8(12):1565-77. doi: 10.1517/17425255.2012.722996. Epub 2012 Sep 13. [Article]
Drug created at June 13, 2005 13:24 / Updated at March 29, 2025 16:10