You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
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
(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
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 pentanoate
Valrubicin
Valrubicina
Valrubicine
Valrubicinum
Valstar
External Identifiers
  • AD 32
  • NSC 246131
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Valstarsolution, concentrate40 mg/mLintravesicalEndo Pharmaceuticals Solutions Inc.1998-10-01Not applicableUs
Valtaxinsolution40 mgintravesicalEndo Pharmaceuticals Solutions Inc2001-04-23Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII2C6NUM6878
CAS number56124-62-0
WeightAverage: 723.651
Monoisotopic: 723.213874712
Chemical FormulaC34H36F3NO13
InChI KeyZOCKGBMQLCSHFP-KQRAQHLDSA-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-{[(2R,4S,5S,6S)-5-hydroxy-6-methyl-4-(2,2,2-trifluoroacetamido)oxan-2-yl]oxy}-7-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-2-yl]ethyl pentanoate
SMILES
[H][C@@]1(C[C@@](O)(CC2=C(O)C3=C(C(O)=C12)C(=O)C1=C(OC)C=CC=C1C3=O)C(=O)COC(=O)CCCC)O[[email protected]]1C[[email protected]](NC(=O)C(F)(F)F)[[email protected]](O)[[email protected]](C)O1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as anthracyclines. These are polyketides containing a tetracenequinone ring structure with a sugar attached by glycosidic linkage.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassAnthracyclines
Sub ClassNot Available
Direct ParentAnthracyclines
Alternative Parents
Substituents
  • Anthracyclinone-skeleton
  • Anthracycline
  • Tetracenequinone
  • 1,4-anthraquinone
  • 9,10-anthraquinone
  • Anthracene
  • Glycosyl compound
  • O-glycosyl compound
  • Tetralin
  • Anisole
  • Phenol ether
  • Aryl ketone
  • Fatty acid ester
  • Alkyl aryl ether
  • Alpha-acyloxy ketone
  • Phenol
  • Benzenoid
  • Oxane
  • Fatty acyl
  • Monosaccharide
  • Tertiary alcohol
  • Vinylogous acid
  • Alpha-hydroxy ketone
  • Carboxylic acid ester
  • Secondary carboxylic acid amide
  • Secondary alcohol
  • Carboxamide group
  • Ketone
  • Monocarboxylic acid or derivatives
  • Acetal
  • Ether
  • Oxacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Polyol
  • Organic nitrogen compound
  • Carbonyl group
  • Organohalogen compound
  • Organofluoride
  • Organonitrogen compound
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Alkyl halide
  • Alkyl fluoride
  • Organic oxygen compound
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
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.
Related Articles
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
PropertyValueProbability
Human Intestinal Absorption+0.8596
Blood Brain Barrier-0.8907
Caco-2 permeable-0.6894
P-glycoprotein substrateSubstrate0.8165
P-glycoprotein inhibitor INon-inhibitor0.5747
P-glycoprotein inhibitor IINon-inhibitor0.5584
Renal organic cation transporterNon-inhibitor0.9348
CYP450 2C9 substrateNon-substrate0.8061
CYP450 2D6 substrateNon-substrate0.7947
CYP450 3A4 substrateSubstrate0.7203
CYP450 1A2 substrateNon-inhibitor0.7239
CYP450 2C9 inhibitorNon-inhibitor0.8228
CYP450 2D6 inhibitorNon-inhibitor0.9016
CYP450 2C19 inhibitorNon-inhibitor0.7565
CYP450 3A4 inhibitorNon-inhibitor0.6895
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7154
Ames testNon AMES toxic0.5421
CarcinogenicityNon-carcinogens0.9272
BiodegradationNot ready biodegradable0.9972
Rat acute toxicity2.8652 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9846
hERG inhibition (predictor II)Inhibitor0.5129
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Endo pharmaceutical solutions inc
Packagers
Dosage forms
FormRouteStrength
Solution, concentrateintravesical40 mg/mL
Solutionintravesical40 mg
Prices
Unit descriptionCostUnit
Valstar 40 mg/ml vial219.96USD ml
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 Solubility0.0325 mg/mLALOGPS
logP2.67ALOGPS
logP4.49ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)8ChemAxon
pKa (Strongest Basic)-3.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area215.22 Å2ChemAxon
Rotatable Bond Count12ChemAxon
Refractivity168.03 m3·mol-1ChemAxon
Polarizability69.2 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot 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 ReferencesNot Available
External Links
ATC CodesL01DB09
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelDownload (80 KB)
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
yes
Actions
intercalation
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
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:7006761 ]
  2. Perabo FG, Muller SC: New agents in intravesical chemotherapy of superficial bladder cancer. Scand J Urol Nephrol. 2005;39(2):108-16. [PubMed:16019763 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Ubiquitin binding
Specific Function:
Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segregation of daughter chromosomes. May play a role in regulating the period length of ARNTL/BMAL1 transcriptional oscillation (By similarity).
Gene Name:
TOP2A
Uniprot ID:
P11388
Molecular Weight:
174383.88 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  2. Perabo FG, Muller SC: New agents in intravesical chemotherapy of superficial bladder cancer. Scand J Urol Nephrol. 2005;39(2):108-16. [PubMed:16019763 ]
Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23