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Details

Stereochemistry ABSOLUTE
Molecular Formula C21H26N2O6
Molecular Weight 402.4409
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of OMBRABULIN

SMILES

COC1=CC=C(\C=C/C2=CC(OC)=C(OC)C(OC)=C2)C=C1NC(=O)[C@@H](N)CO

InChI

InChIKey=IXWNTLSTOZFSCM-YVACAVLKSA-N
InChI=1S/C21H26N2O6/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)/b6-5-/t15-/m0/s1

HIDE SMILES / InChI

Description
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
13.0 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1800 ng/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
750 ng × h/mL
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

T1/2

ValueDoseCo-administeredAnalytePopulation
17.6 min
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

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical 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
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
The development and use of vascular targeted therapy in ovarian cancer.
2017 May
Patents

Patents

Sample Use Guides

AVE8062 (25 mg/m2) Administered Every 3 Weeks
Route of Administration: Intravenous
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.
Name Type Language
OMBRABULIN
INN   WHO-DD  
INN  
Official Name English
AC7700
Code English
AVE-8062
Code English
Ombrabulin [WHO-DD]
Common Name English
(2S)-2-AMINO-3-HYDROXY-N-(2-METHOXY-5-((1Z)-2-(3,4,5-TRIMETHOXYPHENYL)ETHENYL)PHENYL(PROPANAMIDE
Common Name English
AVE8062
Code English
ombrabulin [INN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C67421
Created by admin on Fri Dec 15 17:10:18 GMT 2023 , Edited by admin on Fri Dec 15 17:10:18 GMT 2023
FDA ORPHAN DRUG 334511
Created by admin on Fri Dec 15 17:10:18 GMT 2023 , Edited by admin on Fri Dec 15 17:10:18 GMT 2023
EU-Orphan Drug EU/3/11/853
Created by admin on Fri Dec 15 17:10:18 GMT 2023 , Edited by admin on Fri Dec 15 17:10:18 GMT 2023
Code System Code Type Description
DRUG BANK
DB12882
Created by admin on Fri Dec 15 17:10:18 GMT 2023 , Edited by admin on Fri Dec 15 17:10:18 GMT 2023
PRIMARY
EPA CompTox
DTXSID50939477
Created by admin on Fri Dec 15 17:10:18 GMT 2023 , Edited by admin on Fri Dec 15 17:10:18 GMT 2023
PRIMARY
NCI_THESAURUS
C78480
Created by admin on Fri Dec 15 17:10:18 GMT 2023 , Edited by admin on Fri Dec 15 17:10:18 GMT 2023
PRIMARY
WIKIPEDIA
OMBRABULIN
Created by admin on Fri Dec 15 17:10:18 GMT 2023 , Edited by admin on Fri Dec 15 17:10:18 GMT 2023
PRIMARY
CAS
181816-48-8
Created by admin on Fri Dec 15 17:10:18 GMT 2023 , Edited by admin on Fri Dec 15 17:10:18 GMT 2023
PRIMARY
SMS_ID
100000175010
Created by admin on Fri Dec 15 17:10:18 GMT 2023 , Edited by admin on Fri Dec 15 17:10:18 GMT 2023
PRIMARY
INN
9034
Created by admin on Fri Dec 15 17:10:18 GMT 2023 , Edited by admin on Fri Dec 15 17:10:18 GMT 2023
PRIMARY
FDA UNII
82JB1524Q6
Created by admin on Fri Dec 15 17:10:18 GMT 2023 , Edited by admin on Fri Dec 15 17:10:18 GMT 2023
PRIMARY
PUBCHEM
6918405
Created by admin on Fri Dec 15 17:10:18 GMT 2023 , Edited by admin on Fri Dec 15 17:10:18 GMT 2023
PRIMARY