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Identification
NameValrubicin
Accession NumberDB00385  (APRD00662)
Typesmall molecule
Groupsapproved
Description

Valrubicin (N-trifluoroacetyladriamycin-14-valerate, Valstar®) is a chemotherapy drug used to treat bladder cancer. Valrubicin is a semisynthetic analog of the anthracycline doxorubicin, and is administered by infusion directly into the bladder. [Wikipedia]

Structure
Thumb
Synonyms
SynonymLanguageCode
(8S, 10S)-8-glycoloyl-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-10-[[2,3,6-trideoxy-3-(2,2,2-trifluoroacetamido)-α-L-lyxo-hexopyranosyl]oxy]-5,12-naphthacenedione 8²-valerate Not AvailableWHO
2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-4-({2,3,6-trideoxy-3-[(trifluoroacetyl)amino]hexopyranosyl}oxy)-1,2,3,4,6,11-hexahydrotetracen-2-yl]ethyl pentanoateNot AvailableIUPAC
ValrubicinNot AvailableUSAN, USP 34
ValrubicinaSpanishINN
ValrubicineFrenchINN
ValrubicinumLatinINN
SaltsNot Available
Brand names
NameCompany
ValstarCelltech, Endo
Brand mixturesNot Available
CategoriesNot Available
CAS number56124-62-0
WeightAverage: 723.6437
Monoisotopic: 723.213874858
Chemical FormulaC34H36F3NO13
InChI KeyInChIKey=ZOCKGBMQLCSHFP-ZQUOIQDWSA-N
InChI
InChI=1S/C34H36F3NO13/c1-4-5-9-21(40)49-13-20(39)33(47)11-16-24(19(12-33)51-22-10-17(27(41)14(2)50-22)38-32(46)34(35,36)37)31(45)26-25(29(16)43)28(42)15-7-6-8-18(48-3)23(15)30(26)44/h6-8,14,17,19,22,27,41,43,45,47H,4-5,9-13H2,1-3H3,(H,38,46)/t14?,17?,19-,22?,27?,33-/m0/s1
IUPAC Name
2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-4-{[5-hydroxy-6-methyl-4-(trifluoroacetamido)oxan-2-yl]oxy}-7-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-2-yl]ethyl pentanoate
SMILES
CCCCC(=O)OCC(=O)[C@@]1(O)C[C@H](OC2CC(NC(=O)C(F)(F)F)C(O)C(C)O2)C2=C(C1)C(O)=C1C(=O)C3=C(C(=O)C1=C2O)C(OC)=CC=C3
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassPhenylpropanoids and Polyketides
ClassAnthracyclines
SubclassNot Available
Direct parentAnthracyclines
Alternative parentsTetracenequinones; Anthraquinones; Tetralins; Amino Sugars; Anisoles; Hydroquinones; Fatty Acid Esters; Alkyl Aryl Ethers; Oxanes; Tertiary Alcohols; Polyols; Ketones; Secondary Carboxylic Acid Amides; Secondary Alcohols; Carboxylic Acid Esters; Carboxylic Acids; Dialkyl Ethers; Enolates; Enols; Acetals; Polyamines; Organofluorides; Alkyl Fluorides; Aldehydes
Substituentstetracenequinone; 9,10-anthraquinone; 1,4-anthraquinone; anthracene; acene; amino sugar; tetralin; hydroquinone; phenol ether; anisole; phenol derivative; fatty acid ester; alkyl aryl ether; benzene; oxane; tertiary alcohol; secondary alcohol; secondary carboxylic acid amide; ketone; carboxamide group; polyol; carboxylic acid ester; dialkyl ether; enol; carboxylic acid; ether; carboxylic acid derivative; acetal; polyamine; enolate; amine; organofluoride; alcohol; alkyl halide; alkyl fluoride; organohalogen; aldehyde; carbonyl group; organonitrogen compound
Classification descriptionThis compound belongs to the anthracyclines. These are polyketides containing a tetracenequinone ring structure with a sugar attached by glycosidic linkage.
Pharmacology
IndicationFor the treatment of cancer of the bladder.
PharmacodynamicsValrubicin is a semisynthetic analog of the anthracycline doxorubicin, and is administered by infusion directly into the bladder.
Mechanism of actionValrubicin is an anthracycline that affects a variety of inter-related biological functions, most of which involve nucleic acid metabolism. It readily penetrates into cells, where after DNA intercalation, it inhibits the incorporation of nucleosides into nucleic acids, causes extensive chromosomal damage, and arrests cell cycle in G2. Although valrubicin does not bind strongly to DNA, a principal mechanism of its action, mediated by valrubicin metabolites, is interference with the normal DNA breaking-resealing action of DNA topoisomerase II.
AbsorptionNot Available
Volume of distributionNot Available
Protein binding>99%
Metabolism

Valrubicin is metabolized to two primary metabolites: N-trifluoroacetyladriamycin and N-trifluoroacetyladriamycinol.

SubstrateEnzymesProduct
Valrubicin
    N-trifluoroacetyladriamycinolDetails
    Valrubicin
      N-trifluoroacetyladriamycinDetails
      Route of eliminationNot Available
      Half lifeNot Available
      ClearanceNot Available
      ToxicityThe primary anticipated complications of overdosage associated with intravesical administration would be consistent with irritable bladder symptoms. Myelosuppression is possible if valrubicin is inadvertently administered systemically or if significant systemic exposure occurs following intravesical administration (e.g., in patients with bladder/rupture perforation). The maximum tolerated dose in humans by either intraperitoneal or intravenous administration is 600 mg/m2.
      Affected organisms
      • Humans and other mammals
      PathwaysNot Available
      SNP Mediated EffectsNot Available
      SNP Mediated Adverse Drug ReactionsNot Available
      ADMET
      Predicted ADMET features
      Property Value Probability
      Human Intestinal Absorption + 0.8596
      Blood Brain Barrier - 0.8907
      Caco-2 permeable - 0.6894
      P-glycoprotein substrate Substrate 0.8165
      P-glycoprotein inhibitor I Non-inhibitor 0.5747
      P-glycoprotein inhibitor II Non-inhibitor 0.5584
      Renal organic cation transporter Non-inhibitor 0.9348
      CYP450 2C9 substrate Non-substrate 0.8061
      CYP450 2D6 substrate Non-substrate 0.7947
      CYP450 3A4 substrate Substrate 0.7203
      CYP450 1A2 substrate Non-inhibitor 0.7239
      CYP450 2C9 substrate Non-inhibitor 0.8228
      CYP450 2D6 substrate Non-inhibitor 0.9016
      CYP450 2C19 substrate Non-inhibitor 0.7565
      CYP450 3A4 substrate Non-inhibitor 0.6895
      CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7154
      Ames test Non AMES toxic 0.5421
      Carcinogenicity Non-carcinogens 0.9272
      Biodegradation Not ready biodegradable 0.9972
      Rat acute toxicity 2.8652 LD50, mol/kg Not applicable
      hERG inhibition (predictor I) Weak inhibitor 0.9846
      hERG inhibition (predictor II) Inhibitor 0.5129
      Pharmacoeconomics
      Manufacturers
      • Endo pharmaceutical solutions inc
      Packagers
      Dosage forms
      FormRouteStrength
      LiquidIntravesical
      Prices
      Unit descriptionCostUnit
      Valstar 40 mg/ml vial219.96USDml
      DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
      PatentsNot Available
      Properties
      Statesolid
      Experimental Properties
      PropertyValueSource
      melting point116-117 °CNot Available
      water solubilityinsolubleNot Available
      logP2.2Not Available
      Predicted Properties
      PropertyValueSource
      water solubility3.25e-02 g/lALOGPS
      logP2.67ALOGPS
      logP4.49ChemAxon
      logS-4.3ALOGPS
      pKa (strongest acidic)5.39ChemAxon
      pKa (strongest basic)-3.4ChemAxon
      physiological charge-1ChemAxon
      hydrogen acceptor count12ChemAxon
      hydrogen donor count5ChemAxon
      polar surface area215.22ChemAxon
      rotatable bond count12ChemAxon
      refractivity168.03ChemAxon
      polarizability68.86ChemAxon
      number of rings5ChemAxon
      bioavailability0ChemAxon
      rule of fiveNoChemAxon
      Ghose filterNoChemAxon
      Veber's ruleNoChemAxon
      MDDR-like ruleYesChemAxon
      Spectra
      SpectraNot Available
      References
      Synthesis Reference

      Francesca Scarpitta, Csilla Nemethne Racz, “Crystalline forms of valrubicin and processes for their preparation.” U.S. Patent US20080139490, issued June 12, 2008.

      US20080139490
      General ReferenceNot Available
      External Links
      ResourceLink
      PubChem Compound41744
      PubChem Substance46506642
      ChemSpider38088
      Therapeutic Targets DatabaseDAP000650
      PharmGKBPA164748616
      Drug Product Database2242466
      RxListhttp://www.rxlist.com/cgi/generic2/rubicin.htm
      Drugs.comhttp://www.drugs.com/cdi/valrubicin.html
      WikipediaValrubicin
      ATC CodesL01DB09
      AHFS Codes
      • 10:00.00
      PDB EntriesNot Available
      FDA labelshow(80 KB)
      MSDSNot Available
      Interactions
      Drug Interactions
      Drug
      DocetaxelThe taxane derivative, Docetaxel, may increase Valrubicin toxicity. Consider alternate therapy or monitor for toxic effects.
      NatalizumabValrubicin may increase Natalizumab toxicity. Concurrent therapy should be avoided.
      PaclitaxelThe taxane derivative, Paclitaxel, may increase Valrubicin toxicity. Consider alternate therapy or monitor for toxic effects.
      TrastuzumabTrastuzumab may increase the cardiotoxicity of Valrubicin. Signs and symptoms of cardiac dysfunction should be monitored for frequently. Increased risk of heart failure. Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
      Food InteractionsNot Available

      1. DNA

      Kind: nucleotide

      Organism: Human

      Pharmacological action: yes

      Actions: intercalation

      Components

      Name UniProt ID Details

      References:

      1. Brox L, Gowans B, Belch A: N-trifluoroacetyladriamycin-14-valerate and adriamycin induced DNA damage in the RPMI-6410 human lymphoblastoid cell line. Can J Biochem. 1980 Sep;58(9):720-5. Pubmed
      2. Perabo FG, Muller SC: New agents in intravesical chemotherapy of superficial bladder cancer. Scand J Urol Nephrol. 2005;39(2):108-16. Pubmed

      2. DNA topoisomerase 2-alpha

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: inhibitor

      Components

      Name UniProt ID Details
      DNA topoisomerase 2-alpha P11388 Details

      References:

      1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
      2. Perabo FG, Muller SC: New agents in intravesical chemotherapy of superficial bladder cancer. Scand J Urol Nephrol. 2005;39(2):108-16. Pubmed

      Comments
      Drug created on June 13, 2005 07:24 / Updated on March 14, 2014 15:48