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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
ValstarNot AvailableNot Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Valstarsolution, concentrate40 mg/mLintravesicalEndo Pharmaceuticals Solutions Inc.1998-10-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Valtaxinsolution40 mgintravesicularEndo Pharmaceuticals Solutions IncNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot 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
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
  • Amino sugar
  • Tetralin
  • Aryl ketone
  • Hydroquinone
  • Anisole
  • Alpha-acyloxy ketone
  • Amino saccharide
  • Fatty acid ester
  • Alkyl aryl ether
  • Fatty acyl
  • Benzenoid
  • Oxane
  • Monosaccharide
  • Vinylogous acid
  • Tertiary alcohol
  • Alpha-hydroxy ketone
  • Secondary carboxylic acid amide
  • Secondary alcohol
  • Polyol
  • Ketone
  • Carboxylic acid ester
  • Carboxamide group
  • Oxacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Ether
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Acetal
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Carbonyl group
  • Alkyl halide
  • Alkyl fluoride
  • 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.
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 substrateNon-inhibitor0.8228
CYP450 2D6 substrateNon-inhibitor0.9016
CYP450 2C19 substrateNon-inhibitor0.7565
CYP450 3A4 substrateNon-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
Pharmacoeconomics
Manufacturers
  • Endo pharmaceutical solutions inc
Packagers
Dosage forms
FormRouteStrength
Solutionintravesicular40 mg
Solution, concentrateintravesical40 mg/mL
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)5.39ChemAxon
pKa (Strongest Basic)-3.4ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area215.22 Å2ChemAxon
Rotatable Bond Count12ChemAxon
Refractivity168.03 m3·mol-1ChemAxon
Polarizability68.86 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
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
ATC CodesL01DB09
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelDownload (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