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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 KeyZOCKGBMQLCSHFP-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
Not Available
N-trifluoroacetyladriamycinolDetails
Valrubicin
Not Available
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

Targets

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

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