DT-Web

DB00385 - Valrubicin


Identification
Name Valrubicin
Accession Number DB00385 (APRD00662)
Type small molecule
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
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 723.6437
Groups approved
Monoisotopic Weight 723.213874858
Pharmacology
Indication For the treatment of cancer of the bladder.
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.
Absorption Not Available
Protein binding >99%
Biotransformation Valrubicin is metabolized to two primary metabolites: N-trifluoroacetyladriamycin and N-trifluoroacetyladriamycinol.
Route of elimination Not Available
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.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Docetaxel The taxane derivative, Docetaxel, may increase Valrubicin toxicity. Consider alternate therapy or monitor for toxic effects.
Natalizumab Valrubicin may increase Natalizumab toxicity. Concurrent therapy should be avoided.
Paclitaxel The taxane derivative, Paclitaxel, may increase Valrubicin toxicity. Consider alternate therapy or monitor for toxic effects.
Trastuzumab Trastuzumab 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 Interactions Not Available

Targets


DNA
Name DNA
Gene Name Not Available
Pharmacological action yes
Actions intercalation
References
  • 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
  • Perabo FG, Muller SC: New agents in intravesical chemotherapy of superficial bladder cancer. Scand J Urol Nephrol. 2005;39(2):108-16. - Pubmed
DTHybrid score Not Available
DNA topoisomerase 2-alpha
Name DNA topoisomerase 2-alpha
Gene Name TOP2A
Pharmacological action yes
Actions inhibitor
References
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • Perabo FG, Muller SC: New agents in intravesical chemotherapy of superficial bladder cancer. Scand J Urol Nephrol. 2005;39(2):108-16. - Pubmed
DTHybrid score 0.3555

Predictions


Id Partner name Gene Name Score
477 DNA topoisomerase 4 subunit A parC 0.1361
886 DNA topoisomerase 4 subunit A parC 0.1361
6226 DNA topoisomerase 4 subunit A parC 0.1361
404 DNA gyrase subunit A gyrA 0.1336
6224 DNA gyrase subunit A gyrA 0.1336
4192 DNA topoisomerase 2-beta TOP2B 0.044
4200 Cytochrome P450 1A2 CYP1A2 0.0389
862 Multidrug resistance-associated protein 1 ABCC1 0.0373
4180 DNA-(apurinic or apyrimidinic site) lyase APEX1 0.0305
1588 Multidrug resistance protein 1 ABCB1 0.0292
4512 Cytochrome P450 3A4 CYP3A4 0.024
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0219
118 Organic cation/carnitine transporter 2 SLC22A5 0.0211
1353 DNA topoisomerase 1 TOP1 0.0202
3552 DNA topoisomerase 1 topA 0.0202
588 Chromodomain-helicase-DNA-binding protein 1 CHD1 0.0192
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0189
6137 Multidrug resistance-associated protein 6 ABCC6 0.0163
4119 Cytochrome P450 2D6 CYP2D6 0.015
4118 Cytochrome P450 3A5 CYP3A5 0.0149
2539 Tubulin alpha-1 chain TUBA4A 0.0126
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.012
161 Tubulin beta chain TUBB 0.0117
312 Tubulin beta chain TUB2 0.0117
723 Cytosolic phospholipase A2 PLA2G4A 0.0114
4757 Cytochrome P450 2C9 CYP2C9 0.0112
1729 Solute carrier family 22 member 6 SLC22A6 0.0107
1898 Cytochrome P450 1B1 CYP1B1 0.0105
6016 Cytochrome P450 2C19 CYP2C19 0.0103
833 Organic cation/carnitine transporter 1 SLC22A4 0.0099
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0089
6148 Multidrug resistance-associated protein 7 ABCC10 0.0075
6107 Cytochrome P450 3A7 CYP3A7 0.0072
6144 Solute carrier family 22 member 2 SLC22A2 0.0066
6013 Cytochrome P450 2E1 CYP2E1 0.0065
992 Protein tyrosine kinase 2 beta PTK2B 0.0064
6024 Cytochrome P450 1A1 CYP1A1 0.0053
4120 NADPH--cytochrome P450 reductase POR 0.0053
3947 Xanthine dehydrogenase/oxidase XDH 0.0045
6228 Nuclear receptor coactivator 1 NCOA1 0.0044
6241 Nuclear receptor coactivator 2 NCOA2 0.0043
869 Estrogen receptor beta ESR2 0.0041
776 Bile salt export pump ABCB11 0.0041
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.004
373 Transthyretin TTR 0.0038
6172 ATP-binding cassette sub-family B member 8, mitochondrial ABCB8 0.0036
136 Estrogen receptor ESR1 0.0035
5718 Cytochrome P450 2A6 CYP2A6 0.0034
908 Glutathione S-transferase theta-1 GSTT1 0.0032
337 NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial NDUFS7 0.0029
214 NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial NDUFS3 0.0029
803 NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial NDUFS2 0.0029
6168 Solute carrier family 22 member 16 SLC22A16 0.0029
6861 Alcohol dehydrogenase [NADP+] AKR1A1 0.0026
904 Glutathione S-transferase P GSTP1 0.0025
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0023
5251 Carbonyl reductase [NADPH] 1 CBR1 0.0022
650 Aldo-keto reductase family 1 member C3 AKR1C3 0.0021
290 Prostaglandin G/H synthase 2 PTGS2 0.002
20 Prostaglandin G/H synthase 1 PTGS1 0.0019
2157 NAD(P)H dehydrogenase [quinone] 1 NQO1 0.0019
76 Nitric-oxide synthase, brain NOS1 0.0018
4924 Cytochrome P450 2C8 CYP2C8 0.0016
7 Nitric oxide synthase, inducible NOS2 0.0016
291 Nitric-oxide synthase, endothelial NOS3 0.0015
6030 Cytochrome P450 2B6 CYP2B6 0.0012
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