Vincristine
(Synonyms: 长春新碱,Leurocristine; NSC-67574; 22-Oxovincaleukoblastine) 目录号 : GC38410
Vincristine是一种通过与微管蛋白结合来抑制微管聚合的抑制剂，在无细胞试验中，其 IC50 值为 32μM。Vincristine还可诱导细胞凋亡。
Cas No.:57-22-7
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
| Cell experiment [1]: | |
Cell lines | ALL-2 cells |
Preparation Method | The ALL-2 cells in either G1 or G2/M phases were treated with vehicle (0.1% DMSO) or 100nM Vincristine, harvested at specific times, and DNA content analyzed. |
Reaction Conditions | 100nM; 48h |
Applications | When treated with Vincristine, cells underwent M phase arrest, with 86.4% cells having 4N DNA content within 8h of Vincristine treatment, and by 48h, 50% of cells had <2N DNA content. |
| Animal experiment [2]: | |
Animal models | Vincristine-induced peripheral neuropathy (VIPN) Model |
Preparation Method | Vincristine (<10μg; ip; or 0.5mg/kg; ip) or vehicle (PBS; ip) were administered for five consecutive days, with 2 days break, followed by another five consecutive injections. The highest Vincristine dose (10μg; ip) was administered for four consecutive days, followed by 5 days break and another two injections. Minocycline (25mg/kg; ip) was administered once daily, 3 days before Vincristine administration, and then with each Vincristine injection. |
Dosage form | 1-12 days: <10μg or 0.5mg/kg; 12-25 days: 10μg; ip; 25 days |
Applications | Injection of Vincristine causes swelling and redness of the injected paw as well as a strong dose-dependent infiltration of immune cells to the site of injection. Consistent with the neuro-inflammatory signature, mechanical allodynia was decreased in mice lacking Tlr4, as well as in mice treated with minocycline. |
References: | |
Vincristine is an inhibitor of polymerization of microtubules by binding to tubulin with IC50 of 32μM in a cell-free assay. Vincristine can induces apoptosis[1].
Vincristine (100nM; 48h) induces distinct death programs in primary ALL cells depending on cell cycle phase, and cells in G1 are susceptible to perturbation of interphase microtubules[2].Vincristine (5nM; 4, 8, 24h) triggers a cascade of axon pathology, causing mitochondrial dysfunction that leads to elevated axonal ROS levels and SARM1-dependent axon degeneration[3].Vincristine (0.3-10nM; 48h) and SAHA on T cell leukemic cells resulted in a change in microtubule dynamics contributing to M phase arrest followed by induction of the apoptotic pathway[4].
Vincristine (Pre: <10μg or 0.5mg/kg; Post: 10μg; ip; 25d) causes swelling and redness of the injected paw as well as a strong dose-dependent infiltration of immune cells to the site of injection. Consistent with the neuro-inflammatory signature, mechanical allodynia was decreased in mice lacking Tlr4, as well as in mice treated with minocycline[5].Vincristine (3mg/kg; iv; 1 time) administrated by a single i.p. injection to mice bearing bilateral subcutaneous xenografts Rh12 or Rh18, induces mean growth delay of >120 and >52day, and repopulating fractions of 0.06% and 5%, respectively[6].
References:
[1].Jordan MA, Himes RH, Wilson L. Comparison of the effects of vinblastine, Vincristine, vindesine, and vinepidine on microtubule dynamics and cell proliferation in vitro. Cancer Res. 1985 Jun;45(6):2741-7.
[2].Kothari A, Hittelman W N, Chambers T C. Cell cycle–dependent mechanisms underlie Vincristine-induced death of primary acute lymphoblastic leukemia cells[J]. Cancer research, 2016, 76(12): 3553-3561.
[3].Gomez-Deza J, Slavutsky A L, Nebiyou M, et al. Local production of reactive oxygen species drives Vincristine-induced axon degeneration[J]. Cell Death & Disease, 2023, 14(12): 807.
[4].Chao MW, Lai MJ, Liou JP, Chang YL, Wang JC, Pan SL, Teng CM. The synergic effect of Vincristine and vorinostat in leukemia in vitro and in vivo. J Hematol Oncol. 2015 Jul 10;8:82.
[5].Starobova H, Mueller A, Allavena R, et al. Minocycline prevents the development of mechanical allodynia in mouse models of Vincristine-induced peripheral neuropathy[J]. Frontiers in Neuroscience, 2019, 13: 653.
[6].Baguley BC, Holdaway KM, Thomsen LL, Zhuang L, Zwi LJ. Inhibition of growth of colon 38 adenocarcinoma by vinblastine and colchicine: evidence for a vascular mechanism. Eur J Cancer. 1991;27(4):482-7.
Vincristine是一种通过与微管蛋白结合来抑制微管聚合的抑制剂，在无细胞试验中，其IC50值为 32μM。Vincristine还可诱导细胞凋亡[1]。
Vincristine（100nM；48h）在原代ALL细胞中诱导不同的死亡程序，这取决于细胞周期阶段，G1期细胞容易受到间期微管的干扰[2]。Vincristine（5nM； 4，8 ，24h）会引发一连串的轴突病变，导致线粒体功能障碍，从而导致轴突ROS水平升高和SARM1依赖性轴突变性[3]。Vincristine（0.3-10nM；48h）和SAHA对T细胞白血病细胞的作用导致微管动力学发生变化，导致M期停滞，继而诱导细胞凋亡途径[4]。
Vincristine（1-12 days：<10μg or 0.5mg/kg；12-25 days：10μg； ip； 25d）会导致注射部位的爪子红肿以及免疫细胞的强剂量依赖性浸润。与神经炎症特征相一致的是，缺乏Tlr4的小鼠以及接受米诺环素治疗的小鼠的机械异感减轻[5]。对携带双侧皮下异种移植Rh12或Rh18的小鼠进行一次静脉注射Vincristine（3mg/kg；iv；一次），可诱导平均生长延迟大于120天和大于52天，再植率分别为0.06%和5%[6]。
| Cas No. | 57-22-7 | SDF | |
| 别名 | 长春新碱,Leurocristine; NSC-67574; 22-Oxovincaleukoblastine | ||
| Canonical SMILES | CC[C@@]1(C=CCN2CC3)[C@@]2([H])[C@@]3(C4=CC([C@](C5=C6C7=CC=CC=C7N5)(C[C@](C[C@](CC)(O)C8)([H])C[N@@]8CC6)C(OC)=O)=C(OC)C=C4N9C=O)[C@]9([H])[C@](C(OC)=O)(O)[C@@H]1OC(C)=O | ||
| 分子式 | C46H56N4O10 | 分子量 | 824.96 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C, protect from light |
| 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 | 1.2122 mL | 6.0609 mL | 12.1218 mL |
| 5 mM | 0.2424 mL | 1.2122 mL | 2.4244 mL |
| 10 mM | 0.1212 mL | 0.6061 mL | 1.2122 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。
Genetic factors influencing the development of vincristine-induced neurotoxicity
Expert Opin Drug Metab Toxicol 2021 Feb;17(2):215-226.PMID:33283553DOI:10.1080/17425255.2021.1855141.
Introduction: One of the most common side effects during Vincristine (VCR) use is the establishment of VCR-induced peripheral neuropathy (VIPN). Among several risk factors that can influence the development of VIPN, such as cumulative dose and patient's age, sex, ethnicity, and genetic variants, this review is focused on the genetic variability. Areas covered: A literature research was performed firstly using the following PubMed search string ((((CIPN OR (Vincristine AND neurotoxicity OR (Vincristine AND neuropathy))) AND (polymorphisms OR (genetic variants OR (genetic factors OR (genetic profile OR (pharmacogenetics OR (genome-wide OR (genetic risk OR (expression genotype))))))))))) but also other relevant papers cited by the selected articles were included. Based on the obtained results, we identified two main categories of genes: genes involved in pharmacokinetics (genes related to metabolism and transport) or pharmacodynamics (genes related to mechanism of action) of VCR. Expert opinion: Despite several clinical retrospective studies investigating the possible correlations between patient genotype and VIPN onset, contrasting and inconsistent results are reported. In conclusion, given the clinical relevance of VIPN, further and more focused research would be fundamental in order to identify genetic variants able to predict its development and to allow a safer management of treated patients.
CD38-Directed Vincristine Nanotherapy for Acute Lymphoblastic Leukemia
Biomacromolecules 2022 Jan 10;23(1):377-387.PMID:34913676DOI:10.1021/acs.biomac.1c01342.
Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Although intensive chemotherapy greatly improved the survival rate, it is often accompanied by severe and lifelong side effects as a result of weak ALL selectivity. The intensive and poorly selective chemotherapy is also detrimental to patients' immune system. There is an urgent need to develop more selective and less toxic chemotherapy for ALL. Here, we report daratumumab-polymersome-vincristine (DP-VCR) as a CD38-directed nanotherapy for ALL. DP-VCR showed selective uptake in CD38-positive 697 and Nalm-6-Luc ALL cells and potent anti-ALL activity with an IC50 as low as 0.06 nM VCR, which was 13.7-fold more potent than free VCR. In contrast, no toxicity to human peripheral blood mononuclear cells was detected for DP-VCR even at 108.3 nM VCR. The apoptotic assays confirmed a high selectivity of DP-VCR to CD38-positive ALL cells. DP-VCR exhibited superior treatment of both 697 and Nalm-6-Luc orthotopic ALL models to all controls, as revealed by significant survival benefit and marked reduction of leukemia burden in bone marrow, blood, spleen, and liver. Importantly, DP-VCR induced few side effects. DP-VCR emerges as a safe and potent nanotherapy for CD38-positive ALL.
Vincristine-induced dysphagia
South Med J 1978 Nov;71(11):1364-5.PMID:715485DOI:10.1097/00007611-197811000-00014.
Dysphagia was observed in two patients receiving combination chemotherapy for metastatic carcinoma of the breast. Results of esophagogram and esophagoscopy were unremarkable. Vincristine, an anticancer drug, was incriminated as the causative agent. Cessation of Vincristine therapy resulted in definite improvement. In one patient, inadvertent administration of Vincristine caused prompt recurrence of dysphagia, which again disappeared upon discontinuation of the drug. The major toxicity of Vincristine is neurologic. The exact mechanism for vincristine-induced dysphagia is unknown, but it does appear to be reversible.
Vincristine sulfate liposome injection: a guide to its use in refractory or relapsed acute lymphoblastic leukemia
BioDrugs 2013 Feb;27(1):69-74.PMID:23329395DOI:10.1007/s40259-012-0002-5.
Adult patients with acute lymphoblastic leukemia frequently relapse or are refractory to conventional treatments. The Vincristine sulfate liposome injection (Marqibo(®)) encapsulates the drug in a liposome composed of sphingomyelin and cholesterol to improve tumor drug exposure. At a dose of 2.25 mg/m(2) once weekly, this formulation was associated with an overall response rate of 35 % in adults with Philadelphia chromosome-negative relapsed or refractory disease. There were no new or unexpected toxicities.
Vincristine liposomal--INEX: lipid-encapsulated Vincristine, onco TCS, transmembrane carrier system--vincristine, vincacine, Vincristine sulfate liposomes for injection, VSLI
Drugs R D 2004;5(2):119-23.PMID:15293876DOI:10.2165/00126839-200405020-00012.
INEX Pharmaceuticals is developing a liposomal formulation of Vincristine [Onco TCS, vincacine, VSLI, Vincristine sulfate liposomes for injection] for the treatment of relapsed aggressive non-Hodgkin's lymphoma (NHL) and other cancers. It is being developed using INEX's proprietary drug-delivery technology platform called the transmembrane carrier systems (TCS), which enables the targeted intracellular delivery of various therapeutic agents. Liposomal Vincristine is expected to have certain advantages over the existing standard preparation of Vincristine because the use of TCS technology enables the Vincristine to circulate in the blood for longer, accumulate in the tumour, and be released over an extended period of time at the tumour site. The application of TCS technology to any agent, including Vincristine, has the potential to increase the efficacy and decrease the side effects of the agent. INEX decided in 1998 to focus on gaining approval for liposomal Vincristine in the treatment of relapsed aggressive NHL because no standard therapy was approved for this indication. In 1999, liposomal Vincristine was granted accelerated development status by the US FDA, which enables the FDA to approve it based on the surrogate endpoint of a single clinical trial. In addition, the FDA granted liposomal Vincristine fast track status in August 2000. In April 2001, INEX and Elan Corporation formed a joint venture for the development and commercialisation of liposomal Vincristine, with both companies contributing assets to the venture including worldwide rights to the product and intellectual property rights. The joint venture was called IE Oncology. However, in June 2002, Elan announced that it was going to focus its business strategy on three specific areas, which would not include cancer therapies. INEX announced it had regained 100% ownership of liposomal Vincristine in April 2003, by reacquiring the 19.9% equity interest held by Elan and in addition retaining a fully paid-up licence to Elan's intellectual property pertaining to liposomal Vincristine. All obligations to Elan under the agreement will be met through three milestone payments totalling $8 million. Some of the milestones may be paid in shares valued at the then current market price. In January 2004, INEX and Enzon Pharmaceuticals formed a strategic partnership to develop and commercialise liposomal Vincristine. Under the terms of the agreement, Enzon receives the exclusive North American commercialisation rights for liposomal Vincristine for all indications. INEX will receive upfront and milestone payments as well as a percentage of commercial sales. Additionally, the formation of this partnership triggered a US$3 million payment from INEX to the former joint venture partner, Elan Corporation. Nine clinical trials of liposomal Vincristine are currently being conducted, including one phase I/II trial and eight phase II trials. A phase II/III trial was completed in December 2002. In September 2003, Inex commenced a 'rolling submission' for liposomal Vincristine by submitting the first of three major sections of the NDA to the FDA. The second major section was submitted to the FDA in December 2003. INEX expects to complete the filing with the submission of the clinical section of the NDA in the first quarter of 2004. Dow Jones Newswires reported on 1 October 2001 that the CEO of INEX expects Onco TCS to achieve sales of between $US100 and $US400 million annually for the company. FDA approval was then predicted for late 2002 or early 2003.