Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C34H36F3NO13 |
Molecular Weight | 723.6437 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 6 / 6 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@@]1(C[C@@](O)(CC2=C(O)C3=C(C(=O)C4=C(C=CC=C4OC)C3=O)C(O)=C12)C(=O)COC(=O)CCCC)O[C@H]5C[C@H](NC(=O)C(F)(F)F)[C@H](O)[C@H](C)O5
InChI
InChIKey=ZOCKGBMQLCSHFP-KQRAQHLDSA-N
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
DescriptionSources: https://www.drugbank.ca/drugs/DB00385Curator's Comment: Description was created based on several sources including http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020892s013lbl.pdf
Sources: https://www.drugbank.ca/drugs/DB00385
Curator's Comment: Description was created based on several sources including http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020892s013lbl.pdf
Valrubicin is a semisynthetic analog of the anthracycline doxorubicin, and is administered by infusion directly into the bladder. 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. Valrubicin is FDA approved drug, sold under the trade name Valstar.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1806 |
|||
Target ID: CHEMBL2093867 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1540240 |
0.85 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Valstar Approved UseVALSTAR is indicated for intravesical therapy of BCG-refractory carcinoma in situ (CIS) of the
urinary bladder in patients for whom immediate cystectomy would be associated with
unacceptable morbidity or mortality. Launch Date1998 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
5.2 μg/g |
80 mg/kg single, intravenous dose: 80 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
VALRUBICIN unknown | Mus musculus population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
78 nM × h |
900 mg single, intravesical dose: 900 mg route of administration: Intravesical experiment type: SINGLE co-administered: |
VALRUBICIN plasma | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
161 μg × min/g |
80 mg/kg single, intravenous dose: 80 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
VALRUBICIN unknown | Mus musculus population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
10 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7389059 |
50 mg/kg single, intravenous dose: 50 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
VALRUBICIN plasma | Mus musculus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
0.34 h |
80 mg/kg single, intravenous dose: 80 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
VALRUBICIN unknown | Mus musculus population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1% |
VALRUBICIN plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
900 mg 1 times / week multiple, intravesical Highest studied dose Dose: 900 mg, 1 times / week Route: intravesical Route: multiple Dose: 900 mg, 1 times / week Sources: Page: p.474 |
unhealthy, 66.2 +/- 8.7 n = 9 Health Status: unhealthy Condition: Bladder cancer Age Group: 66.2 +/- 8.7 Sex: M+F Population Size: 9 Sources: Page: p.474 |
Other AEs: Vaginitis, Skin irritation... Other AEs: Vaginitis (11%) Sources: Page: p.474Skin irritation (11%) |
800 mg 1 times / week multiple, intravesical MTD Dose: 800 mg, 1 times / week Route: intravesical Route: multiple Dose: 800 mg, 1 times / week Sources: Page: p.474 |
unhealthy, 66.2 +/- 8.7 n = 7 Health Status: unhealthy Condition: Bladder cancer Age Group: 66.2 +/- 8.7 Sex: M+F Population Size: 7 Sources: Page: p.474 |
|
800 mg 1 times / week multiple, intravesical MTD Dose: 800 mg, 1 times / week Route: intravesical Route: multiple Dose: 800 mg, 1 times / week Sources: Page: p.234 |
unhealthy, 67 n = 14 Health Status: unhealthy Condition: Bladder cancer Age Group: 67 Sex: M+F Population Size: 14 Sources: Page: p.234 |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Skin irritation | 11% | 900 mg 1 times / week multiple, intravesical Highest studied dose Dose: 900 mg, 1 times / week Route: intravesical Route: multiple Dose: 900 mg, 1 times / week Sources: Page: p.474 |
unhealthy, 66.2 +/- 8.7 n = 9 Health Status: unhealthy Condition: Bladder cancer Age Group: 66.2 +/- 8.7 Sex: M+F Population Size: 9 Sources: Page: p.474 |
Vaginitis | 11% | 900 mg 1 times / week multiple, intravesical Highest studied dose Dose: 900 mg, 1 times / week Route: intravesical Route: multiple Dose: 900 mg, 1 times / week Sources: Page: p.474 |
unhealthy, 66.2 +/- 8.7 n = 9 Health Status: unhealthy Condition: Bladder cancer Age Group: 66.2 +/- 8.7 Sex: M+F Population Size: 9 Sources: Page: p.474 |
Sample Use Guides
VALSTAR (Valrubicin) is recommended at a dose of 800 mg administered intravesically once a week for six
weeks. Administration should be delayed at least two weeks after transurethral resection and/or
fulguration. For each instillation, four 5 mL vials (200 mg valrubicin/5 mL vial) should be
allowed to warm slowly to room temperature, but should not be heated. Twenty milliliters of
VALSTAR should then be withdrawn from the four vials and diluted with 55 mL 0.9% Sodium
Chloride Injection, USP providing 75 mL of a diluted VALSTAR solution. A urethral catheter
should then be inserted into the patient's bladder under aseptic conditions, the bladder drained,
and the diluted 75 mL VALSTAR solution instilled slowly via gravity flow over a period of
several minutes. The catheter should then be withdrawn. The patient should retain the drug for
two hours before voiding. At the end of two hours, all patients should void. (Some patients will
be unable to retain the drug for the full two hours.) Patients should be instructed to maintain
adequate hydration following treatment.
Route of Administration:
Other
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2446792
At equimolar concentrations (10 uM), or at concentrations related to their 50% growth-inhibitory values vs CEM (human leukemic lymphoblastic) cells, Valrubicin was consistently found to be more inhibitory than adriamycin of DNA and RNA synthesis, as measured by the incorporation of tritiated thymidine and uridine, respectively, into acid-precipitable fractions relative to untreated controls.
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Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
82194
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LIVERTOX |
1018
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WHO-VATC |
QL01DB09
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NCI_THESAURUS |
C1594
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WHO-ATC |
L01DB09
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2C6NUM6878
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31435
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JJ-54
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2805
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C016163
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SUB05075MIG
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2C6NUM6878
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1708730
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CHEMBL1096885
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DB00385
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m11371
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C1340
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56124-62-0
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454216
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DTXSID9046497
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100000084785
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7288
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VALRUBICIN
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7750
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ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE (PARENT)