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Ganciclovir

July 24, 2017
Common Name

Ganciclovir Description

Ganciclovir is only found in individuals that have used or taken this drug. It is 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. [PubChem]Ganciclovirs 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 cellliar enzyme, thymidine kinase (TK). TK catalyzes phosphorylation of ganciclovir to the monophosphate, which is then subsequently converted into the diphosphate by cellliar guanylate kinase and into the triphosphate by a number of cellliar 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 fality DNA. This is where ganciclovir triphosphate is incorporated into the DNA strand replacing many of the adenosine bases. This reslits 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 cellliar polymerase, and chain elongation resumes when ganciclovir is removed. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source 2-(6-amino-Purin-9-ylmethoxy)-propane-1,3-diolChEBI 2-amino-9-((1,3-Dihydroxypropan-2-yloxy)methyl)-1H-purin-6(9H)-oneChEBI 2-amino-9-((1,3-Dihydroxypropan-2-yloxy)methyl)-3H-purin-6(9H)-oneChEBI 2-amino-9-((1,3-Dihydroxypropan-2-yloxy)methyl)-9H-purin-6-olChEBI 2-amino-9-(2-Hydroxy-1-hydroxymethyl-ethoxymethyl)-1,9-dihydro-purin-6-oneChEBI 2-amino-9-(2-Hydroxy-1-hydroxymethylethoxymethyl)-6,9-dihydro-1H-6-purinoneChEBI 9-((2-Hydroxy-1-(hydroxymethyl)ethoxy)methyl)guanineChEBI 9-(1,3-DIHYDROXY-propoxymethane)guanineChEBI 9-[(1,3-Dihydroxy-2-propoxy)methyl]guanineChEBI GA2ChEBI GanciclovirumChEBI GancyclovirChEBI Ganciclovir sodiumMeSH BIOLF-62MeSH CytoveneMeSH Ganciclovir, monosodium saltMeSH

Chemical Formlia

C9H13N5O4 Average Molecliar Weight

255.2306 Monoisotopic Molecliar Weight

255.096753929 IUPAC Name

2-amino-9-{[(1,3-dihydroxypropan-2-yl)oxy]methyl}-6,9-dihydro-1H-purin-6-one Traditional Name

gancyclovir CAS Registry Number

82410-32-0 SMILES

NC1=NC2=C(N=CN2COC(CO)CO)C(=O)N1

InChI Identifier

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)

InChI Key

IRSCQMHQWWYFCW-UHFFFAOYSA-N Chemical Taxonomy 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

    • Substituents

  • 6-oxopurine
  • Hypoxanthine
  • Aminopyrimidine
  • Pyrimidone
  • Glycerolipid
  • N-substituted imidazole
  • Pyrimidine
  • Azole
  • Imidazole
  • Heteroaromatic compound
  • Vinylogous amide
  • Azacycle
  • Primary amine
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxide
  • Alcohol
  • Organopnictogen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Amine
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound

    • Molecliar Framework

    Aromatic heteropolycyclic compounds External Descriptors

  • oxopurine (CHEBI:465284 )
  • 2-aminopurines (CHEBI:465284 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Antiviral Agents

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Cytoplasm
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting Point250 °CNot Available Boiling PointNot AvailableNot Available Water Solubility1.16e+01 g/LNot Available LogP-1.7Not Available

    Predicted Properties

    Property Value Source Water Solubility11.6 mg/mLALOGPS logP-1.8ALOGPS logP-2.2ChemAxon logS-1.4ALOGPS pKa (Strongest Acidic)10.16ChemAxon pKa (Strongest Basic)1.76ChemAxon Physiological Charge0ChemAxon Hydrogen Acceptor Count7ChemAxon Hydrogen Donor Count4ChemAxon Polar Surface Area134.99 Å2ChemAxon Rotatable Bond Count5ChemAxon Refractivity61.03 m3·mol-1ChemAxon Polarizability24.15 Å3ChemAxon Number of Rings2ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QQ , negativesplash10-0gb9-0090000000-b4bf1558f31e6cd80503View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QQ , negativesplash10-014i-1090000000-80a7b4d22e1375eb8a4dView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QQ , negativesplash10-000j-9610000000-c3053bd735d9f92930bfView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QQ , negativesplash10-007a-9300000000-392c976e03c2a82984ccView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QQ , negativesplash10-00di-9000000000-168468ed262e2df62267View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QQ , positivesplash10-0a4r-0490000000-0a16ac79577fd707fd15View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QQ , positivesplash10-0udi-0920000000-16d50b83e7be32f4db70View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QQ , positivesplash10-0udi-1900000000-2eca31ed3c60988970dcView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QQ , positivesplash10-0udu-2900000000-fd85740333fbb29714c8View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QQ , positivesplash10-01pc-3900000000-81b422bf6764161bcb0fView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-IT , positivesplash10-0udi-0900000000-618946bbba03bdf5db19View in MoNA Predicted LC-MS/MS

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

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

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

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

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

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

    Biological Properties Cellliar Locations

  • Cytoplasm
  • Membrane

    • Biofluid Locations

  • Blood
  • Urine

    • Tissue Location

    Not Available Pathways

    Not Available Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01004

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01004

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB01004 DrugBank Metabolite ID

    Not Available Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    3336 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Ganciclovir NuGOwiki Link

    HMDB15139 Metagene Link

    HMDB15139 METLIN ID

    Not Available PubChem Compound

    3454 PDB ID

    GA2 ChEBI ID

    465284

    Product: HLM006475

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References Not Available

    Transporters

    General function:
    Involved in ion transmembrane transporter activity
    Specific function:
    Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)- N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin- dependent kinase II and LCK tyrosine kinase
    Gene Name:
    SLC22A1
    Uniprot ID:
    O15245
    Molecular weight:
    61187.4
    References
    1. 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. [PubMed:11861798 ]
    General function:
    Involved in ion 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). Mediates the sodium-independent uptake of p- aminohippurate (PAH), ochratoxin (OTA), acyclovir (ACV), 3-azido- 3-deoxythymidine (AZT), cimetidine (CMD), 2,4-dichloro- phenoxyacetate (2,4-D), hippurate (HA), indoleacetate (IA), indoxyl sulfate (IS) and 3-carboxy-4-methyl-5-propyl-2- furanpropionate (CMPF), cidofovir, adefovir, 9-(2- phosphonylmethoxyethyl) guanine (PMEG), 9-(2- phosphonylmethoxyethyl) diaminopurine (PMEDAP) and edaravone sulfate. PAH uptake is inhibited by p- chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate (DEPC), sulindac, diclofenac, carprofen, glutarate and okadaic acid. PAH uptake is inhibited by benzothiazolylcysteine (BTC), S-chlorotrifluoroethylcysteine (CTFC), cysteine S-conjugates S-dichlorovinylcysteine (DCVC), furosemide, steviol, phorbol 12-myristate 13-acetate (PMA), calcium ionophore A23187, benzylpenicillin, furosemide, indomethacin, bumetamide, losartan, probenecid, phenol red, urate, and alpha-ketoglutarate
    Gene Name:
    SLC22A6
    Uniprot ID:
    Q4U2R8
    Molecular weight:
    61815.8
    References
    1. 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. [PubMed:11861798 ]
    General function:
    Involved in transmembrane transport
    Specific function:
    Mediates sodium-independent multispecific organic anion transport. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulfate, allopurinol, 5-fluorouracil, paclitaxel, L-ascorbic acid, salicylate, ethotrexate, and alpha- ketoglutarate
    Gene Name:
    SLC22A7
    Uniprot ID:
    Q9Y694
    Molecular weight:
    60025.0
    References
    1. 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. [PubMed:11861798 ]

    PMID: 10944516

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