| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Targets |
Verubulin exerts its primary antineoplastic activity by binding to the colchicine-binding site on β-tubulin, inhibiting tubulin polymerization and disrupting microtubule dynamics. This leads to mitotic spindle failure, G2/M cell cycle arrest, and apoptosis. As a vascular disrupting agent, it selectively targets immature tumor vasculature, causing acute ischemia and massive tumor cell death. It is not a substrate for multidrug resistance efflux pumps like P-gp, MRP-1, or BCRP-1.
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| ln Vitro |
Verubulin demonstrates potent in vitro cytotoxicity against a broad spectrum of cancer cell lines, including breast, ovarian, melanoma, and glioblastoma. It inhibits microtubule formation with an IC₅₀ of 1.5–3.4 nM. The compound effectively inhibits cancer cell growth regardless of the expression levels of MDR-1, MRP-1, and BCRP-1, indicating its ability to overcome common resistance mechanisms. It also shows potent activity against cells with mutated tubulin isoforms.
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| ln Vivo |
In vivo, Verubulin exhibits potent and broad-spectrum antitumor activity. In mouse xenograft models, MPC-6827 (2.5–10 mg/kg) significantly reduces tumor growth in various subcutaneously implanted tumor lines, including MX-1 breast, OVCAR-3 ovarian, MIA PaCa-2 pancreatic, MCF-7 breast, HT-29 colon, and MDA-MB-435 melanoma. The compound also disrupts newly formed blood vessels in xenografts, leading to tumor necrosis and regression.
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| Enzyme Assay |
Non-cellular assays for Verubulin involve assessing its ability to inhibit tubulin polymerization in a cell-free system. Purified bovine brain tubulin is incubated with varying concentrations of Verubulin in polymerization buffer (containing GTP and glycerol) at 37°C. The extent of polymerization is measured spectrophotometrically by monitoring the increase in turbidity at 340 nm over time. The IC₅₀ for inhibition of microtubule formation is determined from dose-response curves. Competitive binding assays using [³H]colchicine can confirm that Verubulin binds to the colchicine site on tubulin.
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| Cell Assay |
In vitro cellular assays for Verubulin involve treating a panel of human cancer cell lines with the compound and assessing cell viability, proliferation, and apoptosis. Cells are typically seeded in 96-well plates and exposed to varying concentrations of Verubulin (0.1 nM–10 µM) for 48–72 hours. Cell viability is measured using MTT or CellTiter-Glo® luminescent assays. Apoptosis is assessed by flow cytometry using Annexin V/PI staining or by measuring caspase-3/7 activity. Cell cycle analysis is performed by propidium iodide staining to confirm G2/M phase arrest. The compound's ability to circumvent multidrug resistance is evaluated by comparing IC₅₀ values in isogenic cell pairs with and without P-gp overexpression.
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| Animal Protocol |
In vivo animal experiments with Verubulin are conducted in immunocompromised mice bearing subcutaneous xenografts of human cancer cell lines. Once tumors reach approximately 100-200 mm³, mice are randomized and treated with Verubulin, typically via intravenous administration at doses of 2.5, 5, or 10 mg/kg on various schedules (e.g., daily for 5 days, or weekly). Tumor growth inhibition is monitored by caliper measurements twice weekly. At study termination, tumors are excised for histopathological analysis, including assessment of vascular disruption (by CD31 staining), apoptosis (by TUNEL assay), and proliferation (by Ki-67 immunohistochemistry). Pharmacodynamic studies may also measure tubulin polymerization in tumor tissue.
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| ADME/Pharmacokinetics |
Verubulin demonstrates excellent blood-brain barrier (BBB) penetration, achieving a high brain-to-plasma ratio of 30:1, which is attributed to its lack of affinity for P-glycoprotein efflux transporters. In a Phase I clinical trial, the mean plasma half-life of verubulin was 3.2 hours (SD = 0.82). The compound is primarily metabolized by hepatic CYP450 enzymes, and its pharmacokinetics are linear over the dose range studied. The high brain exposure makes it particularly suitable for the treatment of glioblastoma and brain metastases.
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| Toxicity/Toxicokinetics |
In a Phase I trial of verubulin combined with carboplatin in patients with relapsed glioblastoma, four patients (21%) experienced a grade 3 or greater adverse event, including hypesthesia, cerebral ischemia, anemia, and thrombocytopenia. The maximum tolerated dose was determined to be 3.3 mg/m². The combination was found to be safe and well-tolerated, with no cerebral hemorrhage observed. Common side effects included fatigue, nausea, and myelosuppression. The compound is classified as toxic and should be handled only by trained personnel.
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| References | |
| Additional Infomation |
Antitumor drug; a small molecule microtubule formation inhibitor, not a substrate of the multidrug resistance pump. Velublin is a quinazoline derivative with potential antitumor activity. Velublin binds to tubulin and inhibits its polymerization, thereby blocking microtubule formation, leading to disordered spindle assembly during mitosis, cell cycle arrest at the G2/M phase, and ultimately cell death. This drug is not a substrate of many multidrug resistance ABC transporter subtypes, and therefore may be helpful in treating multidrug-resistant tumors. Furthermore, as a vascular disruptor, verublin specifically disrupts tumor microvessels, leading to acute ischemia and massive tumor cell death. Additionally, verublin can cross the blood-brain barrier and accumulate in the brain. See also: Velublin hydrochloride (note moved to).
Drug Indications Studied for the treatment of brain cancer, lung cancer, melanoma, and solid tumors. Verubulin (MPC-6827; Azixa) was advanced to clinical trials, including a Phase II study for the treatment of subjects with recurrent glioblastoma (NCT00719823). In a Phase I trial combining verubulin with carboplatin, two patients achieved at least a partial response, and five had stable disease; the 6-month progression-free survival rate was 21%. Beyond oncology, its high affinity for tubulin has enabled its development as a PET radiotracer, [11C]verubulin, for imaging microtubules in neurological disorders such as Alzheimer's disease. The compound is available for research purposes from various suppliers. |
| Molecular Formula |
C17H17N3O
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|---|---|
| Molecular Weight |
279.336383581162
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| Exact Mass |
279.137
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| CAS # |
827031-83-4
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| Related CAS # |
Verubulin hydrochloride;917369-31-4
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| PubChem CID |
11414799
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
398.7±38.0 °C at 760 mmHg
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| Melting Point |
86-90 °C
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| Flash Point |
194.9±26.8 °C
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| Vapour Pressure |
0.0±0.9 mmHg at 25°C
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| Index of Refraction |
1.652
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| LogP |
2.02
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
21
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| Complexity |
330
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1C2C(=CC=CC=2)C(N(C)C2C=CC(OC)=CC=2)=NC=1C
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| InChi Key |
SNHCRNMVYDHVDT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H17N3O/c1-12-18-16-7-5-4-6-15(16)17(19-12)20(2)13-8-10-14(21-3)11-9-13/h4-11H,1-3H3
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| Chemical Name |
N-(4-methoxyphenyl)-N,2-dimethylquinazolin-4-amine
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| Synonyms |
Verubulin; MPC-6827; 827031-83-4; N-(4-Methoxyphenyl)-N,2-dimethylquinazolin-4-amine; MX-128495; Verubulina; MPC6827
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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) |
DMSO : ~100 mg/mL (~357.99 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (7.45 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (7.45 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (7.45 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5799 mL | 17.8993 mL | 35.7987 mL | |
| 5 mM | 0.7160 mL | 3.5799 mL | 7.1597 mL | |
| 10 mM | 0.3580 mL | 1.7899 mL | 3.5799 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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