| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg | |||
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| Targets |
Ombrabulin targets tubulin and disrupts microtubules in tumor endothelial cells by binding to the colchicine binding site. As a vascular-disrupting agent (VDA), it leads to tumor vascular collapse and ischemic necrosis. It is a tubulin polymerization inhibitor that selectively disrupts the tubulin cytoskeleton of endothelial cells, resulting in antivascular effects and tumor growth inhibition.
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| ln Vitro |
The MTT test is utilized to investigate the impact of Ombrabulin (AC-7700) on the viability of tumor or endothelial cells. For the tumor cell lines (HeyA8, SKOV3ip1, and HeyA8-MDR), ombrabulin's half-life (IC50) is 7–20 nM, while it is 10 nM for mouse mesenteric endothelial cells (MMEC). In comparison to each agent alone, Ombrabulin (AC-7700)/Docetaxel exhibits a considerably lower IC50 than either agent alone (P<0.005, all cell lines) according to a comparative analysis of the nonlinear least-squares regression of the dose-response curves. Compared to docetaxel alone, the cytotoxicity of cetaxel to tumor and endothelial cells is two to four times higher when combined with ombrabulin (AC-7700)[1].
In vitro, Ombrabulin acts as a tubulin polymerization inhibitor and vascular-disrupting agent. It selectively disrupts the tubulin cytoskeleton of endothelial cells, leading to antivascular effects. As a derivative of CA-4 phosphate, it inhibits tubulin polymerization and induces G2/M arrest in cancer cells. Its in vitro activity is assessed by measuring its effects on microtubule organization and cell viability in cancer cell lines. |
| ln Vivo |
Prior to conducting therapeutic trials, the tolerance of two weekly intravenous, intraperitoneal, or subcutaneous injections of Ombabulin (AC-7700) at dosages ranging from 10 to 100 mg/kg is evaluated in nude mice (n = 3 per group). The IV and SC methods are not followed up on because of issues with tail vein necrosis or skin. With doses up to 100 mg/kg, the intraperitoneal route is well tolerated. Afterwards, pilot studies are conducted to ascertain the minimum dosage required for in vivo medicinal effectiveness. Tumor cell injection-bearing nude mice (n = 5 per group) are administered with vehicle or Ombrabulin 10, 30, 50, and 100 mg/kg twice weekly intraperitoneally (i.p.) for three weeks beginning seven days after the tumor cell injection. When comparing the 30 mg/kg group to the vehicle control group, there is a 65% decrease in tumor weight (P<0.02). The dosage of 10 mg/kg is ineffective. The 30 mg/kg dose is chosen for further therapy trials since the antitumor effects at doses higher than 30 mg/kg are not appreciably better[1].
In vivo activity of Ombrabulin has been demonstrated in preclinical and clinical studies, where it shows potent antitumor activity. As a vascular-disrupting agent, it strongly inhibits tumor blood flow and suppresses tumor growth in various tissues and organs. It has been investigated for the treatment of non-rhabdomyosarcoma soft tissue sarcomas and rhabdomyosarcoma. |
| Enzyme Assay |
The in vitro enzyme/receptor binding (cell-free) assay for Ombrabulin involves measuring its binding to tubulin and inhibition of tubulin polymerization. These assays use purified tubulin protein and measure the extent of polymerization in the presence of the compound. The compound binds to the colchicine binding site on tubulin, preventing the assembly of microtubules. Inhibitory potency (IC50) is determined by assessing the reduction in polymerization using spectrophotometric methods.
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| Cell Assay |
In vitro cellular assays for Ombrabulin are performed using endothelial cells and cancer cell lines. These assays measure the compound's ability to disrupt the tubulin cytoskeleton, induce cell cycle arrest, and cause apoptosis. The compound's effects on microtubule organization are assessed by immunofluorescence staining of tubulin. Cytotoxicity is measured using standard cell viability assays, demonstrating its potent anticancer and antivascular activity.
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| Animal Protocol |
In vivo animal studies for Ombrabulin are conducted in mouse xenograft models of various cancers. These studies typically involve administration of the compound, followed by assessment of tumor growth inhibition, tumor blood flow, and vascular disruption. The compound's ability to inhibit tumor growth in various tissues and organs has been demonstrated in these models. Pharmacokinetic-pharmacodynamic relationships are also evaluated to optimize dosing regimens.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Ombrabulin are characterized by improved water solubility compared to combretastatin A4, supporting systemic administration. As a vascular-disrupting agent, it is designed to reach tumor vasculature and exert its effects. The compound's pharmacokinetic profile includes distribution to tumor tissues and rapid clearance from the circulation. Its improved solubility and oral bioavailability support its use in cancer therapy.
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| Toxicity/Toxicokinetics |
Toxicology studies of Ombrabulin have been conducted to support its clinical development. As a vascular-disrupting agent, its toxicology profile includes effects on cardiovascular function and potential for off-target effects on normal vasculature. Preclinical toxicology studies include acute and repeat-dose toxicity assessments, as well as genotoxicity and safety pharmacology evaluations. The compound has been investigated in clinical studies for various cancer indications.
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| References | |
| Additional Infomation |
Obrabulin has been used in clinical trials for the treatment of various diseases, including sarcomas, tumors, solid tumors, malignant tumors, and advanced solid tumors. Obrabulin is a synthetic water-soluble analogue of combrestatin A4, extracted from the South African willow (Combretum caffrum), and possesses potential angiogenic and antitumor activities. Obrabulin binds to the colchicine binding site of endothelial cell microtubules, inhibiting microtubule polymerization and inducing mitotic arrest and apoptosis in endothelial cells. As apoptotic endothelial cells detach from their matrix, tumor blood vessels collapse; acute interruption of tumor blood flow may lead to tumor necrosis.
Drug Indications Treatment of non-rhabdomyosarcoma soft tissue sarcomas, treatment of rhabdomyosarcoma Ombrabulin, also known as AVE8062, is a derivative of CA-4 phosphate that shows antivascular effects through selective disruption of the tubulin cytoskeleton of endothelial cells. It has been investigated for the treatment of non-rhabdomyosarcoma soft tissue sarcomas and rhabdomyosarcoma. The compound's vascular-disrupting mechanism offers a unique approach to cancer therapy by targeting tumor blood vessels and inducing ischemic necrosis. |
| Molecular Formula |
C21H26N2O6
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|---|---|
| Molecular Weight |
402.45
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| Exact Mass |
402.179
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| CAS # |
181816-48-8
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| Related CAS # |
Ombrabulin hydrochloride;253426-24-3
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| PubChem CID |
6918405
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| Appearance |
Colorless to light yellow ointment
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| Density |
1.0±0.1 g/cm3
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| Boiling Point |
191.0±13.0 °C at 760 mmHg
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| Flash Point |
59.2±12.0 °C
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| Vapour Pressure |
0.7±0.4 mmHg at 25°C
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| Index of Refraction |
1.415
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| LogP |
0.53
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
29
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| Complexity |
517
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O=C(NC1=CC(/C=C\C2=CC(OC)=C(OC)C(OC)=C2)=CC=C1OC)[C@@H](N)CO
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| InChi Key |
IXWNTLSTOZFSCM-YVACAVLKSA-N
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| InChi Code |
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
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| Chemical Name |
(2S)-2-amino-3-hydroxy-N-[2-methoxy-5-[(Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenyl]propanamide
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| Synonyms |
AVE 8062 AVE-8062 AVE8062
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4848 mL | 12.4239 mL | 24.8478 mL | |
| 5 mM | 0.4970 mL | 2.4848 mL | 4.9696 mL | |
| 10 mM | 0.2485 mL | 1.2424 mL | 2.4848 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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