OMBRABULIN

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 Search

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
Sources: https://www.drugbank.ca/drugs/DB12882
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

Targets

Primary Target	Pharmacology	Condition	Potency
Tubulin 69 Target ID: CHEMBL2095182 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26852340	Inhibitor 8297		13.0 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Sarcoma 14 Sources: https://clinicaltrials.gov/ct2/show/NCT00699517	Primary	Phase III 656	Unknown Approved Use Unknown
Ovarian cancer 157 Sources: https://clinicaltrials.gov/ct2/show/NCT01332656	Primary	Phase II 1132	Unknown Approved Use Unknown
Non-small cell lung cancer 206 Sources: https://clinicaltrials.gov/ct2/show/NCT01263886	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

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

T_1/2

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
inhibitor 1587

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 1478 CYP1A2 1524

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23833302/	no	yes (co-administration study) Comment: The dimethylxanthine to caffeine ratio was 1.17. Sources: https://pubmed.ncbi.nlm.nih.gov/23833302/
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23833302/	no	yes (co-administration study) Comment: Midazolam rdecreased Cmax and AUCt by 23% and 17%. Sources: https://pubmed.ncbi.nlm.nih.gov/23833302/
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23833302/	weak	yes (co-administration study) Comment: estimated omeprazole versus 5-hydroxyomeprazole ratio of 1.26 Sources: https://pubmed.ncbi.nlm.nih.gov/23833302/

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00BFOF	https://www.1pchem.com/search?query=1P00BFOF
AK Scientific	9526AA	https://aksci.com/item_detail.php?cat=9526AA
AbovChem LLC	HY-14797	http://www.abovchem.com/pc/en/product_list.aspx?wd=HY-14797
Alfa Chemistry	ACM181816488	http://www.alfa-chemistry.com/search.aspx?q=ACM181816488
Angene	AGN-PC-0QC3DK	http://www.angenechemical.com/productshow/AGN-PC-0QC3DK.html
BLD Pharm	BD246767	http://www.bldpharm.com/search/Search.html?keyword=BD246767
BLD Pharm	BD630593	http://www.bldpharm.com/search/Search.html?keyword=BD630593
BOC Sciences	181816-48-8	http://www.bocsci.com/description.asp?cas=181816-48-8
Chem Scene	CS-5451	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-5451
MedChem Express	HY-18256	https://www.medchemexpress.com/search.html?q=HY-18256&ft=&fa=&fp=
MolPort	MolPort-046-418-352	https://www.molport.com/shop/molecule-link/MolPort-046-418-352
Molnova	M12793	https://www.molnova.com/en/serch-list.html?keywords=M12793
Molnova	M13754	https://www.molnova.com/en/serch-list.html?keywords=M13754
MuseChem	I008448	https://www.musechem.com/product/I008448.html
ShangHai Biochempartner	BCP000903	http://www.biochempartner.com/search_BCP000903
ShangHai Biochempartner	BCP07754	http://www.biochempartner.com/search_BCP07754
Toronto Research Chemicals	O633403	https://www.trc-canada.com/product-detail/?CatNum=O633403
eMolecules	275170625	https://orderbb.emolecules.com/search/#?query=275170625
eMolecules	300772124	https://orderbb.emolecules.com/search/#?query=300772124
eMolecules	44845785	https://orderbb.emolecules.com/search/#?query=44845785
eMolecules	75542275	https://orderbb.emolecules.com/search/#?query=75542275
mcule	MCULE-1992303632	https://mcule.com/MCULE-1992303632/
mcule	MCULE-4551655806	https://mcule.com/MCULE-4551655806/
mcule	MCULE-5771510649	https://mcule.com/MCULE-5771510649/

PubMed

Title	Date	PubMed
The development and use of vascular targeted therapy in ovarian cancer.	2017 May	28238563

Patents

Sample Use Guides

In Vivo Use Guide

AVE8062 (25 mg/m2) Administered Every 3 Weeks

Route of Administration: Intravenous

In Vitro Use Guide

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

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