Details
Stereochemistry | ACHIRAL |
Molecular Formula | C17H17N3O.ClH |
Molecular Weight | 315.797 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.COC1=CC=C(C=C1)N(C)C2=NC(C)=NC3=CC=CC=C23
InChI
InChIKey=VYUWDIKZJLOZJL-UHFFFAOYSA-N
InChI=1S/C17H17N3O.ClH/c1-12-18-16-7-5-4-6-15(16)17(19-12)20(2)13-8-10-14(21-3)11-9-13;/h4-11H,1-3H3;1H
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/17575155Curator's Comment: description was created based on several sources, including:
http://adisinsight.springer.com/drugs/800022153 | http://www.prnewswire.com/news-releases/new-data-suggests-improved-tumor-response-for-the-combination-of-azixa-and-immune-checkpoint-inhibitors-in-the-treatment-of-cancer-300291030.html
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17575155
Curator's Comment: description was created based on several sources, including:
http://adisinsight.springer.com/drugs/800022153 | http://www.prnewswire.com/news-releases/new-data-suggests-improved-tumor-response-for-the-combination-of-azixa-and-immune-checkpoint-inhibitors-in-the-treatment-of-cancer-300291030.html
Veribulin is a novel microtubule destabilizer that both functions as a potent cytotoxin and acts as a vascular disrupting agent (VDA). It binds to the same (or nearby) sites on β-tubulin as colchicine. It is capable of evading multidrug resistance pumps and, thus, achieves high CNS concentrations. It is efficacious in multiple xenograft models without CNS toxicity. Veribulin had previously demonstrated pre-clinical and clinical activity in multiple tumor types. Veribulin is in phase II clinical trial for the treatment of Glioblastoma and Malignant melanoma.
CNS Activity
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: Tubulin beta Sources: https://www.ncbi.nlm.nih.gov/pubmed/17575155 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
21.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21159616 |
3.3 mg/m² 1 times / week multiple, intravenous dose: 3.3 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
VERUBULIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
30.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21159616 |
3.9 mg/m² 1 times / week multiple, intravenous dose: 3.9 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
VERUBULIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
62 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21159616 |
4.5 mg/m² 1 times / week multiple, intravenous dose: 4.5 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
VERUBULIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
116.8 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21159616 |
3.3 mg/m² 1 times / week multiple, intravenous dose: 3.3 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
VERUBULIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
139.3 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21159616 |
3.9 mg/m² 1 times / week multiple, intravenous dose: 3.9 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
VERUBULIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
183.6 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21159616 |
4.5 mg/m² 1 times / week multiple, intravenous dose: 4.5 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
VERUBULIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
6.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21159616 |
3.3 mg/m² 1 times / week multiple, intravenous dose: 3.3 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
VERUBULIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
7.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21159616 |
3.9 mg/m² 1 times / week multiple, intravenous dose: 3.9 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
VERUBULIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
5.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21159616 |
4.5 mg/m² 1 times / week multiple, intravenous dose: 4.5 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
VERUBULIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
4.5 mg/m2 1 times / week multiple, intravenous Highest studied dose Dose: 4.5 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 4.5 mg/m2, 1 times / week Sources: Page: p.3413 |
unhealthy, ADULT n = 7 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 7 Sources: Page: p.3413 |
DLT: Myocardial infarction... Dose limiting toxicities: Myocardial infarction (grade 3, 14.3%) Sources: Page: p.3413 |
3.3 mg/m2 1 times / week multiple, intravenous MTD Dose: 3.3 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 3.3 mg/m2, 1 times / week Sources: Page: p.3413 |
unhealthy, ADULT n = 13 Health Status: unhealthy Condition: cance Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 13 Sources: Page: p.3413 |
|
3.3 mg/m2 1 times / week multiple, intravenous MTD Dose: 3.3 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 3.3 mg/m2, 1 times / week Sources: Page: p.338 |
unhealthy, ADULT n = 31 Health Status: unhealthy Condition: glioblastoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 31 Sources: Page: p.338 |
Disc. AE: Myocardial infarction... AEs leading to discontinuation/dose reduction: Myocardial infarction (grade 4, 3.2%) Sources: Page: p.338 |
3.9 mg/m2 1 times / week multiple, intravenous Studied dose Dose: 3.9 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 3.9 mg/m2, 1 times / week Sources: Page: p.3413 |
unhealthy, ADULT n = 6 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: Page: p.3413 |
DLT: Myocardial infarction... Dose limiting toxicities: Myocardial infarction (grade 3, 16.7%) Sources: Page: p.3413 |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Myocardial infarction | grade 3, 14.3% DLT |
4.5 mg/m2 1 times / week multiple, intravenous Highest studied dose Dose: 4.5 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 4.5 mg/m2, 1 times / week Sources: Page: p.3413 |
unhealthy, ADULT n = 7 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 7 Sources: Page: p.3413 |
Myocardial infarction | grade 4, 3.2% Disc. AE |
3.3 mg/m2 1 times / week multiple, intravenous MTD Dose: 3.3 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 3.3 mg/m2, 1 times / week Sources: Page: p.338 |
unhealthy, ADULT n = 31 Health Status: unhealthy Condition: glioblastoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 31 Sources: Page: p.338 |
Myocardial infarction | grade 3, 16.7% DLT |
3.9 mg/m2 1 times / week multiple, intravenous Studied dose Dose: 3.9 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 3.9 mg/m2, 1 times / week Sources: Page: p.3413 |
unhealthy, ADULT n = 6 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: Page: p.3413 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24740196
Verubulin was administered at 3.3 mg/m(2) as a 2-h intravenous infusion once weekly for 3 consecutive weeks in a 4-week cycle.
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19296653
Verubulin was highly active in HCT116 and SNU-398 cells with EC50 values of 3 nM and 2 nM, respectively, similar to its high activity in T47D cells.
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Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
290809
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NCI_THESAURUS |
C25974
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11638255
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UU-21
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DTXSID80238682
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917369-31-4
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C64782
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CHEMBL492399
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C522974
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33380QZ0QW
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300000044542
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DBSALT002603
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ACTIVE MOIETY
SUBSTANCE RECORD