1. Cell Cycle/DNA Damage
    Cytoskeleton
  2. Microtubule/Tubulin

Ombrabulin hydrochloride (Synonyms: AVE8062; AVE8062A; AC7700; AVE-8062; AVE-8062A; AC-7700; AVE 8062; AVE 8062A; AC 7700)

Cat. No.: HY-18256 Purity: 99.57%
Data Sheet SDS Handling Instructions

Ombrabulin hydrochloride is a derivative of CA-4 phosphate, which is known to exhibit antivascular effects through selective disruption of the tubulin cytoskeleton of endothelial cells.

For research use only. We do not sell to patients.
Ombrabulin hydrochloride Chemical Structure

Ombrabulin hydrochloride Chemical Structure

CAS No. : 253426-24-3

Size Price Stock Quantity
10 mM * 1 mL in DMSO $338 In-stock
1 mg $150 In-stock
5 mg $350 In-stock
10 mg $500 In-stock
50 mg $1500 In-stock
100 mg $2100 In-stock
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Other Forms of Ombrabulin hydrochloride:

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Description

Ombrabulin hydrochloride is a derivative of CA-4 phosphate, which is known to exhibit antivascular effects through selective disruption of the tubulin cytoskeleton of endothelial cells.

IC50 & Target

tubulin[1]

In Vitro

The effect of Ombrabulin (AVE8062) on endothelial or tumor cell viability is examined using the MTT assay. The IC50 of Ombrabulin for the mouse mesenteric endothelial cells (MMEC) is 10 nM and ranges between 7 and 20 nM for the tumor cell lines (HeyA8, SKOV3ip1, and HeyA8-MDR). Comparative analysis of the nonlinear least-squares regression of the dose-response curves for each agent alone and combination Ombrabulin /Docetaxel show a significantly lower IC50 than either agent alone (P<0.005, all cell lines). The cytotoxicity of Docetaxel is 2- to 4-fold greater in combination with Ombrabulin for the endothelial and tumor cells compared with Docetaxel alone[1].

In Vivo

Before performing therapy experiments, the tolerability of various doses of Ombrabulin (AVE8062) ranging from 10 to 100 mg/kg is tested given twice weekly via i.v., i.p., or s.c. routes in nude mice (n=3 per group). The i.v. and s.c. routes are not pursued further due to problems with skin or tail vein necrosis. The i.p. route is well tolerated with doses up to 100 mg/kg. Next, preliminary experiments are done to determine the lowest dose for in vivo therapeutic efficacy. Starting 7 days after tumor cell injection, nude mice (n=5 per group) bearing HeyA8 ovarian cancer cells are treated with either vehicle or Ombrabulin 10, 30, 50, and 100 mg/kg twice weekly i.p. for 3 weeks. There is 65% reduction in tumor weight in the 30 mg/kg group compared with the vehicle control group (P<0.02). The 10 mg/kg dose is not effective. The antitumor effects at doses >30 mg/kg are not significantly better; therefore, the 30 mg/kg dose is selected for subsequent therapy experiments[1].

Clinical Trial
NCT Number Sponsor Condition Start Date Phase
NCT01907685 Sanofi Advanced Neoplastic Disease June 2006 Phase 1
NCT01063946 Sanofi Neoplasms, Malignant January 2010 Phase 1
NCT00968916 Sanofi Solid Tumor September 2009 Phase 1
NCT01193595 Sanofi Neoplasms, Malignant September 2010 Phase 1
NCT00719524 Sanofi Neoplasms July 2008 Phase 1
NCT01021150 Sanofi Neoplasms, Malignant March 2010 Phase 1
NCT01263886 Sanofi Non-small Cell Lung Cancer February 2011 Phase 2
NCT01095302 Sanofi Neoplasms, Malignant May 2010 Phase 1
NCT00699517 Sanofi Sarcoma June 2008 Phase 3
NCT01293630 Sanofi Advanced Solid Tumors January 2011 Phase 1
NCT01332656 Sanofi Ovarian Cancer Recurrent May 2011 Phase 2
NCT01907685 Sanofi Advanced Neoplastic Disease June 2006 Phase 1
NCT01063946 Sanofi Neoplasms, Malignant January 2010 Phase 1
NCT00968916 Sanofi Solid Tumor September 2009 Phase 1
NCT01193595 Sanofi Neoplasms, Malignant September 2010 Phase 1
NCT00719524 Sanofi Neoplasms July 2008 Phase 1
NCT01021150 Sanofi Neoplasms, Malignant March 2010 Phase 1
NCT01263886 Sanofi Non-small Cell Lung Cancer February 2011 Phase 2
NCT01095302 Sanofi Neoplasms, Malignant May 2010 Phase 1
NCT00699517 Sanofi Sarcoma June 2008 Phase 3
NCT01293630 Sanofi Advanced Solid Tumors January 2011 Phase 1
NCT01332656 Sanofi Ovarian Cancer Recurrent May 2011 Phase 2
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References
Preparing Stock Solutions
Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
1 mM 2.2784 mL 11.3921 mL 22.7842 mL
5 mM 0.4557 mL 2.2784 mL 4.5568 mL
10 mM 0.2278 mL 1.1392 mL 2.2784 mL
Cell Assay
[1]

The capacity of Ombrabulin (AVE8062) to modulate MMEC and HeyA8 cell cycle as well as apoptosis is analyzed by flow cytometry. In all assays, 3×106 tumor cells are seeded into Petri dishes and allowed to adhere overnight. The cultures are then washed with PBS and treated with regular medium (negative control) or medium containing Docetaxel, Ombrabulin (HeyA8, 20 nM; MMEC 10 nM), or Ombrabulin plus Docetaxel. For cell cycle analyses, tumor cells are collected by trypsinization and pooled with the cells floating in the medium. The cell suspensions are centrifuged for 5 min at 1,500 rpm at room temperature, then washed and fixed with ethanol. For apoptosis analysis, cells are incubated overnight in 50 μL of DNA labeling solution (10 μL of reaction buffer, 0.75 μL of TdT enzyme, 8 μL of FITC-dUTP, and 32.25 μL of distilled water) at room temperature. Following the addition of rinse buffer, samples are centrifuged, washed, and fixed in ethanol. All samples are then washed with PBS, then resuspended in propidium iodide (50 μg/mL) and RNase A (20 μg/mL) in PBS for 30 min at room temperature. Stained cells are analyzed on an EPICS XL flow cytometer. The low-level gate is set at the base of the G1 peak and the percentages of cells within the G1 and G2-M phases of the cell cycle are determined by analysis with Multicycle[1].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

Ombrabulin (AVE8062) is dissolved in PBS (pH 5) (Mice)[1].

Mice[1]
Female athymic nude mice (6-8 weeks old) are used. For in vivo injection, tumor cells are trypsinized, centrifuged at 1,000 rpm ×7 min at 4°C, washed twice, and resuspended in serum-free HBSS at a concentration of 5×106 cells/mL (SKOV3ip1 and HeyA8-MDR) and 1.25×106 cells/mL (HeyA8). Tumors are established by i.p. injection of cells. Ombrabulin therapy is initiated 7 or 17 days after cell line injection. Mice (n=10 per group) are randomly assigned to the following treatment groups: (a) PBS 200 μL, i.p. weekly; (b) Ombrabulin 30 mg/kg [dissolved in PBS (pH 5)] i.p. twice weekly; (c) Docetaxel 2 mg/kg (HeyA8 and HeyA8-MDR) or 1.4 mg/kg (SKOV3ip1) i.p. weekly; (d) Ombrabulin plus Docetaxel (both drugs given at the doses and frequency described above for each drug alone). The dose of Ombrabulin used in these experiments is optimized from dose-escalation studies against tumor growth. Mice are monitored for signs of adverse effects and tumors are harvested after treatment (range 2-5 weeks). The mouse weight, tumor weight, number of tumor nodules, and volume of ascites are recorded at necropsy.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
M.Wt

438.9

Formula

C₂₁H₂₇ClN₂O₆

CAS No.

253426-24-3

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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Product Name:
Ombrabulin hydrochloride
Cat. No.:
HY-18256
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