Maytansine
(Synonyms: 美坦新,NSC 153858) 目录号 : GC62205
An ansa macrolide with anticancer activity
Cas No.:35846-53-8
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Maytansine is an ansa macrolide originally isolated from M. serrata that has anticancer activity.1 It inhibits the growth of L1210, L-5178-Y, and P388 murine leukemia cells (EC50s = 0.6, 12, and 1.5 nM, respectively). Maytansine (20 ?M) inhibits erythrocyte and brain tubulin polymerization.2 In vivo, maytansine (0.025-0.1 mg/kg) increases survival in a P388 murine leukemia model.1 It has also been used in the synthesis of cytotoxic payload moieties of antibody-drug conjugates (ADCs).3
1.Wolpert-Defilippes, M.K., Adamson, R.H., Cysyk, R.L., et al.Initial studies on the cytotoxic action of maytansine, a novel ansa macrolideBiochem. Pharmacol.24(6)751-754(1975) 2.Luduena, R.F., Anderson, W.H., Prasad, V., et al.Interactions of vinblastine and maytansine with tubulinAnn. N. Y. Acad. Sci.466718-732(1986) 3.Yaghoubi, S., Karimi, M.H., Lotfinia, M., et al.Potential drugs used in the antibody-drug conjugate (ADC) architecture for cancer therapyJ. Cell Physiol.235(1)31-64(2020)
| Cas No. | 35846-53-8 | SDF | |
| 别名 | 美坦新,NSC 153858 | ||
| 分子式 | C34H46ClN3O10 | 分子量 | 692.2 |
| 溶解度 | 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.4447 mL | 7.2233 mL | 14.4467 mL |
| 5 mM | 0.2889 mL | 1.4447 mL | 2.8893 mL |
| 10 mM | 0.1445 mL | 0.7223 mL | 1.4447 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。
Biomimetic Nanoerythrosome-Coated Aptamer-DNA Tetrahedron/Maytansine Conjugates: pH-Responsive and Targeted Cytotoxicity for HER2-Positive Breast Cancer
Adv Mater 2022 Nov;34(46):e2109609.PMID:35064993DOI:10.1002/adma.202109609.
DNA materials have emerged as potential nanocarriers for targeted cancer therapy to precisely deliver cargos with specific purposes. The short half-life and low bioavailability of DNA materials due to their interception by the reticuloendothelial system and blood clearance further limit their clinical translation. This study employs an HER2-targeted DNA-aptamer-modified DNA tetrahedron (HApt-tFNA) as a drug delivery system, and combines Maytansine (DM1) to develop the HApt-DNA tetrahedron/DM1 conjugate (HApt-tFNA@DM1, HTD, HApDC) for targeted therapy of HER2-positive cancer. To optimize the pharmacokinetics and tumor-aggregation of HTD, a biomimetic camouflage is applied to embed HTD. The biomimetic camouflage is constructed by merging the erythrocyte membrane with pH-responsive functionalized synthetic liposomes, thus with excellent performance of drug delivery and tumor-stimulated drug release. The hybrid erythrosome-based nanoparticles show better inhibition of HER2-positive cancer than other drug formulations and exhibit superior biosafety. With the strengths of precise delivery, increased drug loading, sensitive tumor probing, and prolonged circulation time, the HApDC represents a promising nanomedicine to treat HER2-positive tumors. Notably, this study developsa dual-targeting nanoparticle by combining pH-sensitive camouflage and HApDC, initiating an important step toward the development and application of DNA-based medicine and biomimetic cell membrane materials in cancer treatment and other potential biological applications.
Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer
N Engl J Med 2019 Feb 14;380(7):617-628.PMID:30516102DOI:10.1056/NEJMoa1814017.
Background: Patients who have residual invasive breast cancer after receiving neoadjuvant chemotherapy plus human epidermal growth factor receptor 2 (HER2)-targeted therapy have a worse prognosis than those who have no residual cancer. Trastuzumab emtansine (T-DM1), an antibody-drug conjugate of trastuzumab and the cytotoxic agent emtansine (DM1), a Maytansine derivative and microtubule inhibitor, provides benefit in patients with metastatic breast cancer that was previously treated with chemotherapy plus HER2-targeted therapy. Methods: We conducted a phase 3, open-label trial involving patients with HER2-positive early breast cancer who were found to have residual invasive disease in the breast or axilla at surgery after receiving neoadjuvant therapy containing a taxane (with or without anthracycline) and trastuzumab. Patients were randomly assigned to receive adjuvant T-DM1 or trastuzumab for 14 cycles. The primary end point was invasive disease-free survival (defined as freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause). Results: At the interim analysis, among 1486 randomly assigned patients (743 in the T-DM1 group and 743 in the trastuzumab group), invasive disease or death had occurred in 91 patients in the T-DM1 group (12.2%) and 165 patients in the trastuzumab group (22.2%). The estimated percentage of patients who were free of invasive disease at 3 years was 88.3% in the T-DM1 group and 77.0% in the trastuzumab group. Invasive disease-free survival was significantly higher in the T-DM1 group than in the trastuzumab group (hazard ratio for invasive disease or death, 0.50; 95% confidence interval, 0.39 to 0.64; P<0.001). Distant recurrence as the first invasive-disease event occurred in 10.5% of patients in the T-DM1 group and 15.9% of those in the trastuzumab group. The safety data were consistent with the known safety profile of T-DM1, with more adverse events associated with T-DM1 than with trastuzumab alone. Conclusions: Among patients with HER2-positive early breast cancer who had residual invasive disease after completion of neoadjuvant therapy, the risk of recurrence of invasive breast cancer or death was 50% lower with adjuvant T-DM1 than with trastuzumab alone. (Funded by F. Hoffmann-La Roche/Genentech; KATHERINE ClinicalTrials.gov number, NCT01772472 .).
Targeted delivery of Maytansine to liver cancer cells via galactose-modified supramolecular two-dimensional glycomaterial
Chem Commun (Camb) 2022 Apr 19;58(32):5029-5032.PMID:35373789DOI:10.1039/d1cc06809a.
A two-dimensional (2D) glycomaterial for targeted delivery of Maytansine to liver cancer cells was developed. Host-guest interaction between a galactosyl dye and human serum albumin (HSA) produces supramolecular galactoside-HSA conjugates, which are then used to coat 2D MoS2. The 2D glycomaterial was shown to be capable of the targeted delivery of Maytansine to a liver cancer cell line that highly expresses a galactose receptor, resulting in greater cytotoxicity than Maytansine alone.
Maytansine and cellular metabolites of antibody-maytansinoid conjugates strongly suppress microtubule dynamics by binding to microtubules
Mol Cancer Ther 2010 Oct;9(10):2689-99.PMID:20937594DOI:10.1158/1535-7163.MCT-10-0644.
Maytansine is a potent microtubule-targeted compound that induces mitotic arrest and kills tumor cells at subnanomolar concentrations. However, its side effects and lack of tumor specificity have prevented successful clinical use. Recently, antibody-conjugated Maytansine derivatives have been developed to overcome these drawbacks. Several conjugates show promising early clinical results. We evaluated the effects on microtubule polymerization and dynamic instability of Maytansine and two cellular metabolites (S-methyl-DM1 and S-methyl-DM4) of antibody-maytansinoid conjugates that are potent in cells at picomolar levels and that are active in tumor-bearing mice. Although S-methyl-DM1 and S-methyl-DM4 inhibited polymerization more weakly than Maytansine, at 100 nmol/L they suppressed dynamic instability more strongly than Maytansine (by 84% and 73%, respectively, compared with 45% for Maytansine). However, unlike Maytansine, S-methyl-DM1 and S-methyl-DM4 induced tubulin aggregates detectable by electron microscopy at concentrations ≥2 μmol/L, with S-methyl-DM4 showing more extensive aggregate formation than S-methyl-DM1. Both Maytansine and S-methyl-DM1 bound to tubulin with similar K(D) values (0.86 ± 0.2 and 0.93 ± 0.2 μmol/L, respectively). Tritiated S-methyl-DM1 bound to 37 high-affinity sites per microtubule (K(D), 0.1 ± 0.05 μmol/L). Thus, S-methyl-DM1 binds to high-affinity sites on microtubules 20-fold more strongly than vinblastine. The high-affinity binding is likely at microtubule ends and is responsible for suppression of microtubule dynamic instability. Also, at higher concentrations, S-methyl-DM1 showed low-affinity binding either to a larger number of sites on microtubules or to sedimentable tubulin aggregates. Overall, the Maytansine derivatives that result from cellular metabolism of the antibody conjugates are themselves potent microtubule poisons, interacting with microtubules as effectively as or more effectively than the parent molecule.
Spatial profiling of Maytansine during the germination process of Maytenus senegalensis seeds
Fitoterapia 2017 Jun;119:51-56.PMID:28385670DOI:10.1016/j.fitote.2017.03.014.
The ecological role of Maytansine, an important antineoplastic and antimicrobial compound with high cytotoxicity, particularly as a chemical defense compound has remained elusive since its discovery in the 1970s in Maytenus and Putterlickia plants. In the present study, we have used MALDI-imaging-HRMS to visualize the occurrence as well as spatial and temporal distribution of Maytansine in a Maytenus senegalensis plant, seeds obtained from the mother plant during seeding stage, through the germination of the seeds, and finally up to the establishment of seedlings (or daughter plants). Although the mother plant was devoid of Maytansine, the bioactive compound was found to be distributed in the cotyledons and the endosperm of the seeds with an augmented accretion towards the seed coat. Furthermore, Maytansine was always detected in the emerging seedlings, particularly the cortex encompassing the radicle, hypocotyl, and epicotyl. The typical pattern of accumulation of Maytansine not only in the seeds but also during germination provides a proof-of-concept that M. senegalensis is ecologically primed to trigger the production of Maytansine in vulnerable tissues such as seeds during plant reproduction. By utilizing Maytansine as chemical defense compound against predators and/or pathogens, the plant can ensure viability of the seeds and successful germination, thus leading to the next generation of daughter plants.