NAV

Valrubicin

Identification

Summary

Valrubicin is an anthracycline used intravesically in the treatment of BCG-resistant bladder carcinoma.

Brand Names
Valstar
Generic Name
Valrubicin
DrugBank Accession Number
DB00385
Background

Valrubicin (N-trifluoroacetyladriamycin-14-valerate) is a chemotherapy drug commonly marketed under the trade name VALSTAR. It is a semisynthetic analog of the doxorubicin, which is an anthracycline drug. Used in the treatment of the bladder cancer, valrubicin is administered by direct infusion into the bladder.

Type
Small Molecule
Groups
Approved
Structure
Similar Structures
Weight
Average: 723.651
Monoisotopic: 723.213874712
Chemical Formula
C34H36F3NO13
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
External IDs
  • AD 32
  • AD-32
  • NSC 246131
  • NSC-246131

Pharmacology

Indication

For the treatment of cancer of the bladder.

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Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Valrubicin is an anticancer agent.

Mechanism of action

Valrubicin 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.

TargetActionsOrganism
ADNA
intercalation
Humans
ADNA topoisomerase 2-alpha
inhibitor
Humans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

>99%

Metabolism

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

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Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

The 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.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
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Darbepoetin alfaThe risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Valrubicin.
ErythropoietinThe risk or severity of Thrombosis can be increased when Erythropoietin is combined with Valrubicin.
MargetuximabThe risk or severity of cardiotoxicity can be increased when Margetuximab is combined with Valrubicin.
Methoxy polyethylene glycol-epoetin betaThe risk or severity of Thrombosis can be increased when Methoxy polyethylene glycol-epoetin beta is combined with Valrubicin.
PeginesatideThe risk or severity of Thrombosis can be increased when Peginesatide is combined with Valrubicin.
TrastuzumabThe risk or severity of cardiotoxicity can be increased when Trastuzumab is combined with Valrubicin.
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Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ValstarSolution, concentrate40 mg/1mLIntravesicalEndo Pharmaceuticals Solutions Inc.1998-10-01Not applicableUS flag
ValtaxinSolution40 mg / mLIntravesicalEndo Pharmaceuticals Solutions Inc.2001-04-232017-08-01Canada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Valrubicin Intravesical SolutionSolution, concentrate40 mg/1mLIntravesicalLeucadia Pharmaceuticals2019-04-23Not applicableUS flag

Categories

ATC Codes
L01DB09 — Valrubicin
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This 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.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Anthracyclines
Sub Class
Not Available
Direct Parent
Anthracyclines
Alternative Parents
Tetracenequinones / Anthraquinones / O-glycosyl compounds / Tetralins / Anisoles / Aryl ketones / Alkyl aryl ethers / Alpha-acyloxy ketones / Fatty acid esters / Oxanes
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Substituents
1,4-anthraquinone / 9,10-anthraquinone / Acetal / Alcohol / Alkyl aryl ether / Alkyl fluoride / Alkyl halide / Alpha-acyloxy ketone / Alpha-hydroxy ketone / Anisole
show 37 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
2C6NUM6878
CAS number
56124-62-0
InChI Key
ZOCKGBMQLCSHFP-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[C@H]1C[C@H](NC(=O)C(F)(F)F)[C@H](O)[C@H](C)O1

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 References
Not Available
PubChem Compound
454216
PubChem Substance
46506642
ChemSpider
399974
RxNav
31435
ChEBI
135876
ChEMBL
CHEMBL1096885
ZINC
ZINC000049783788
Therapeutic Targets Database
DAP000650
PharmGKB
PA164748616
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Valrubicin
FDA label
Download (80 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3TerminatedTreatmentIn Situ Carcinoma / Non-muscle Invasive Bladder Cancer (NMIBC) / Urothelial Carcinoma1
3Unknown StatusTreatmentBladder Cancer, Cancer1
2CompletedTreatmentBladder Cancer, Cancer2
2, 3CompletedTreatmentBladder Cancer, Cancer / In Situ Carcinoma1
1CompletedTreatmentUrothelial Carcinoma1

Pharmacoeconomics

Manufacturers
  • Endo pharmaceutical solutions inc
Packagers
  • Endo Pharmaceuticals Inc.
  • Primapharm Inc.
Dosage Forms
FormRouteStrength
Solution, concentrateIntravesical40 mg/1mL
SolutionIntravesical40 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.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)116-117 °CNot Available
water solubilityinsolubleNot Available
logP2.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0325 mg/mLALOGPS
logP2.67ALOGPS
logP4.49ChemAxon
logS-4.4ALOGPS
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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

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Details1. DNA
Kind
Nucleotide
Organism
Humans
Pharmacological action
Yes
Actions
Intercalation
DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.
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. [Article]
  2. Perabo FG, Muller SC: New agents in intravesical chemotherapy of superficial bladder cancer. Scand J Urol Nephrol. 2005;39(2):108-16. [Article]
Details2. DNA topoisomerase 2-alpha
Kind
Protein
Organism
Humans
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 segr...
Gene Name
TOP2A
Uniprot ID
P11388
Uniprot Name
DNA topoisomerase 2-alpha
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. [Article]
  2. Perabo FG, Muller SC: New agents in intravesical chemotherapy of superficial bladder cancer. Scand J Urol Nephrol. 2005;39(2):108-16. [Article]

Drug created at June 13, 2005 13:24 / Updated at August 09, 2022 10:05