Verubulin
(Synonyms: (4-甲氧基苯基)(甲基)(2-甲基喹唑啉-4-基)胺,MPC 6827) 目录号 : GC37900
Verubulin hydrochloride(MPC 6827 hydrochloride) is a microtubule destabilizer and vascular disrupting agent that achieve high brain concentration relative to plasma in animals.
Cas No.:827031-83-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Verubulin hydrochloride(MPC 6827 hydrochloride) is a microtubule destabilizer and vascular disrupting agent that achieve high brain concentration relative to plasma in animals.
Verubulin hydrochloride is the hydrochloride of compound Verubulin. Verubulin(MPC-6827) is a potent inhibitors of cancer cell growth, with GI50 values of 3-6 nM in T47D, HCT116 and SNU-398 cells.[2]
Verubulin(MPC-6827) has excellent blood brain barrier penetration, and is highly efficacious in a MX-1 breast tumor model. [2]
[1] Chamberlain MC, et al. J Neurooncol. 2014 Jun;118(2):335-343. [1] Sirisoma N, et al. J Med Chem. 2009 Apr 23;52(8):2341-51.
| Cas No. | 827031-83-4 | SDF | |
| 别名 | (4-甲氧基苯基)(甲基)(2-甲基喹唑啉-4-基)胺,MPC 6827 | ||
| Canonical SMILES | CC1=NC(N(C2=CC=C(OC)C=C2)C)=C3C=CC=CC3=N1 | ||
| 分子式 | C17H17N3O | 分子量 | 279.34 |
| 溶解度 | DMSO: 125 mg/mL (447.48 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.5799 mL | 17.8993 mL | 35.7987 mL |
| 5 mM | 0.716 mL | 3.5799 mL | 7.1597 mL |
| 10 mM | 0.358 mL | 1.7899 mL | 3.5799 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Preliminary Evaluations of [11C]Verubulin: Implications for Microtubule Imaging With PET
Front Neurosci 2021 Sep 8;15:725873.PMID:34566568DOI:10.3389/fnins.2021.725873.
[11C]Verubulin (a.k.a.[11C]MCP-6827), [11C]HD-800 and [11C]colchicine have been developed for imaging microtubules (MTs) with positron emission tomography (PET). The objective of this work was to conduct an in vivo comparison of [11C]Verubulin for MT imaging in mouse and rat brain, as well as an in vitro study with this radiotracer in rodent and human Alzheimer's Disease tissue. Our preliminary PET imaging studies of [11C]Verubulin in rodents revealed contradictory results between mouse and rat brain uptake under pretreatment conditions. In vitro autoradiography with [11C]Verubulin showed an unexpected higher uptake in AD patient tissue compared with healthy controls. We also conducted the first comparative in vivo PET imaging study with [11C]Verubulin, [11C]HD-800 and [11C]colchicine in a non-human primate. [11C]Verubulin and [11C]HD-800 require pharmacokinetic modeling and quantification studies to understand the role of how these radiotracers bind to MTs before translation to human use.
Phase I trial of Verubulin (MPC-6827) plus carboplatin in patients with relapsed glioblastoma multiforme
J Neurooncol 2012 Nov;110(2):257-64.PMID:22932984DOI:10.1007/s11060-012-0964-7.
Verubulin (MPC-6827) is a microtubule-destabilizing agent that achieves high concentrations in the brain. Verubulin disrupts newly formed blood vessels in xenografts. We determined the safety and tolerability of Verubulin administered in combination with carboplatin in patients with relapsed glioblastoma multiforme (GBM). Three pre-selected doses of Verubulin were tested: 2.1, 2.7, and 3.3 mg/m(2) in a standard "3+3" design. Verubulin was given every second week of a 6-week cycle in the 2.1 mg/m(2) cohort or weekly for 3 weeks of a 4-week cycle in subsequent cohorts. Carboplatin was administered intravenously at an area under the curve (AUC) dosage 4 every 2 weeks for the 2.1 mg/m(2) cohort or on day 1 of each 4-week cycle in subsequent cohorts. Nineteen patients with GBM in first or second relapse were enrolled. Four patients (21 %) experienced a grade 3 or greater verubulin- or carboplatin-related adverse event, including hypesthesia, cerebral ischemia, anemia, and thrombocytopenia. The mean plasma half life of Verubulin was 3.2 h (SD = 0.82). Two patients achieved at least a partial response by Macdonald criteria. One of these patients remains progression free and off treatment more than 24 months beyond his initiation of Verubulin. Five patients had stable disease. Median progression-free survival (PFS) across all patients was 8 weeks, and the 6-month PFS rate was 21 %. The combination of Verubulin at the previously determined single-agent maximum tolerated dose of 3.3 mg/m(2) with carboplatin in patients with recurrent/refractory GBM is safe and well tolerated. In this patient population with a highly vascularized tumor, no cerebral hemorrhage was observed.
Effects of the tumor-vasculature-disrupting agent Verubulin and two heteroaryl analogues on cancer cells, endothelial cells, and blood vessels
ChemMedChem 2014 Apr;9(4):847-54.PMID:24678059DOI:10.1002/cmdc.201300531.
Two analogues of the discontinued tumor vascular-disrupting agent Verubulin (Azixa®, MPC-6827, 1) featuring benzo-1,4-dioxan-6-yl (compound 5 a) and N-methylindol-5-yl (compound 10) residues instead of the para-anisyl group on the 4-(methylamino)-2-methylquinazoline pharmacophore, were prepared and found to exceed the antitumor efficacy of the lead compound. They were antiproliferative with single-digit nanomolar IC50 values against a panel of nine tumor cell lines, while not affecting nonmalignant fibroblasts. Indole 10 surpassed Verubulin in seven tumor cell lines including colon, breast, ovarian, and germ cell cancer cell lines. In line with docking studies indicating that compound 10 may bind the colchicine binding site of tubulin more tightly (Ebind =-9.8 kcal mol(-1) ) than Verubulin (Ebind =-8.3 kcal mol(-1) ), 10 suppressed the formation of vessel-like tubes in endothelial cells and destroyed the blood vessels in the chorioallantoic membrane of fertilized chicken eggs at nanomolar concentrations. When applied to nude mice bearing a highly vascularized 1411HP germ cell xenograft tumor, compound 10 displayed pronounced vascular-disrupting effects that led to hemorrhages and extensive central necrosis in the tumor.
A phase 2 trial of Verubulin for recurrent glioblastoma: a prospective study by the Brain Tumor Investigational Consortium (BTIC)
J Neurooncol 2014 Jun;118(2):335-343.PMID:24740196DOI:10.1007/s11060-014-1437-y.
Treatment options are limited for recurrent glioblastoma (GBM). Verubulin is a microtubule destabilizer and vascular disrupting agent that achieve high brain concentration relative to plasma in animals. Adults with recurrent GBM who failed prior standard therapy were eligible. The primary endpoint was 1-month progression-free survival (PFS-1) for bevacizumab refractory (Group 2) and 6-month progression-free survival (PFS-6) for bevacizumab naïve patients (Group 1). Verubulin was administered at 3.3 mg/m(2) as a 2-h intravenous infusion once weekly for 3 consecutive weeks in a 4-week cycle. The planned sample size was 34 subjects per cohort. 56 patients (37 men, 19 women) were enrolled, 31 in Group 1 and 25 in Group 2. The PFS-6 for Group 1 was 14% and the PFS-1 for Group 2 was 20%. Median survival from onset of treatment was 9.5 months in Group 1 and 3.4 months in Group 2. Best overall response was partial response (n = 3; 10% in Group 1; n = 1; 4.2% in Group 2) and stable disease (n = 7; 23% in Group 1; n = 5; 21% in Group 2). In Group 1, 38.7% of patients experienced a serious adverse event; however only 3.2% were potentially attributable to study drug. In Group 2, 44% of patients experienced a serious adverse event although none were attributable to study drug. Accrual was terminated early for futility. Single agent Verubulin, in this dose and schedule, is well tolerated, associated with moderate but tolerable toxicity but has limited activity in either bevacizumab naïve or refractory recurrent GBM.
Discovery of novel quinazolines as potential anti-tubulin agents occupying three zones of colchicine domain
Bioorg Chem 2019 Mar;83:380-390.PMID:30408650DOI:10.1016/j.bioorg.2018.10.027.
A series of novel quinazolines as tubulin inhibitors occupying three zones of colchicine domain have been designed and synthesized inspired by the recently disclosed crystal structure of Verubulin analogue 6 with tubulin. Among the newly synthesized compounds, 19c showed noteworthy potency against K562, HepG2, KB, HCT-8 and MDB-MB-231 cancer cells. In vitro microtubule polymerization assays identified 19c as a potent tubulin assembly inhibitor, the binding mode of which with tubulin was confirmed by molecular modeling studies to occupy three zones of tubulin domain. Furthermore, 19c disrupted the intracellular microtubule network, caused G2/M phase arrest, induced cell apoptosis and depolarized mitochondria of K562 cells. 19c also reduced the cell migration and disrupted the capillary-like tube formation of human umbilical vein endothelial cells (HUVECs). Importantly, 19c significantly and dose dependently inhibited tumor growth in H22 liver cancer xenograft mouse model. All these results suggested that 19c deserves further research as a novel and potential anti-tubulin agent for the treatment of cancers.