Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C21H26N2O6.ClH |
| Molecular Weight | 438.902 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 1 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.COC1=CC=C(\C=C/C2=CC(OC)=C(OC)C(OC)=C2)C=C1NC(=O)[C@@H](N)CO
InChI
InChIKey=UQNRTPFLTRZEIM-MRWUDIQNSA-N
InChI=1S/C21H26N2O6.ClH/c1-26-17-8-7-13(9-16(17)23-21(25)15(22)12-24)5-6-14-10-18(27-2)20(29-4)19(11-14)28-3;/h5-11,15,24H,12,22H2,1-4H3,(H,23,25);1H/b6-5-;/t15-;/m0./s1
| Molecular Formula | ClH |
| Molecular Weight | 36.461 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
| Molecular Formula | C21H26N2O6 |
| Molecular Weight | 402.4409 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 1 |
| Optical Activity | UNSPECIFIED |
DescriptionCurator's Comment: The description was created based on several sources, including
https://clinicaltrials.gov/ct2/show/NCT00699517 | https://www.ncbi.nlm.nih.gov/pubmed/27566973 | https://clinicaltrials.gov/ct2/show/NCT01332656 | https://www.ncbi.nlm.nih.gov/pubmed/25864104 | https://clinicaltrials.gov/ct2/show/NCT01263886 | https://clinicaltrials.gov/ct2/show/NCT01263886
Curator's Comment: The description was created based on several sources, including
https://clinicaltrials.gov/ct2/show/NCT00699517 | https://www.ncbi.nlm.nih.gov/pubmed/27566973 | https://clinicaltrials.gov/ct2/show/NCT01332656 | https://www.ncbi.nlm.nih.gov/pubmed/25864104 | https://clinicaltrials.gov/ct2/show/NCT01263886 | https://clinicaltrials.gov/ct2/show/NCT01263886
Ombrabulin is an experimental drug candidate discovered by Ajinomoto and further developed by Sanofi-Aventis for cancer treatment.
Ombrabulin is a synthetic water-soluble analog of combretastatin A4, derived from the South African willow bush (Combretum caffrum), with potential vascular-disrupting and antineoplastic activities. Ombrabulin binds to the colchicine binding site of endothelial cell tubulin, inhibiting tubulin polymerization and inducing mitotic arrest and apoptosis in endothelial cells. As apoptotic endothelial cells detach from their substrate, tumor blood vessels collapse; the acute disruption of tumor blood flow may result in tumor necrosis. Ombrabulin has been used in trials studying the treatment of Sarcoma, Neoplasms, Solid Tumor, Neoplasms, Malignant, and Advanced Solid Tumors, among others. In January 2013, Sanofi said it discontinued development of Ombrabulin after disappointing results from phase III clinical trials.
Originator
Approval Year
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1800 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24477603 |
50 mg/m² single, intravenous dose: 50 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
OMBRABULIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
750 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24477603 |
50 mg/m² single, intravenous dose: 50 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
OMBRABULIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
17.6 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24477603 |
50 mg/m² single, intravenous dose: 50 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
OMBRABULIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no | yes (co-administration study) Comment: The dimethylxanthine to caffeine ratio was 1.17. |
|||
| no | yes (co-administration study) Comment: Midazolam rdecreased Cmax and AUCt by 23% and 17%. |
|||
| weak | yes (co-administration study) Comment: estimated omeprazole versus 5-hydroxyomeprazole ratio of 1.26 |
Sample Use Guides
The ovarian cancer cell lines HeyA8 and SKOV3ip1 were used for activity evaluation. Two thousand tumor cells were seeded into 38-mm2 wells of flat-bottomed 96-well plates in triplicate and allowed to adhere overnight. Cultures were then washed and regular medium (negative control) or medium containing docetaxel with or without AVE8062 (Ombrabulin) were added. After 72 h, the number of metabolically active cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Dose-response curves for growth inhibition were generated as a percentage of untreated control. IC50 was determined by nonlinear leastsquares regression (Prism, Graph Pad Software, Inc.). Combination assays were done by using the IC50 of AVE8062 (7–20 nmol/L, depending on the cell line) with escalating doses of docetaxel. To assess the potential effect of combination AVE8062 and docetaxel therapy relative to either agent alone, dose-response curves were compared.
| Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 15:52:33 GMT 2023
by
admin
on
Fri Dec 15 15:52:33 GMT 2023
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| Record UNII |
KXZ9NDO6H0
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| Record Status |
Validated (UNII)
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