Larotaxel
(Synonyms: XRP9881) 目录号 : GC36424
Larotaxel (XRP9881) 是一种紫杉烷类似物，具有抗紫杉烷抗性乳腺癌的临床前活性。Larotaxel (XRP9881) 通过促进微管蛋白装配和稳定微管发挥其细胞毒性作用，并最终通过细胞凋亡导致细胞死亡。Larotaxel (XRP9881) 具有穿越血脑屏障的能力，对 P-糖蛋白 1 的亲和力比 Docetaxel 低得多。
Cas No.:156294-36-9
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
Larotaxel (XRP9881) is a taxane analogue with preclinical activity against taxane-resistant breast cancer. Larotaxel (XRP9881) exerts its cytotoxic effect by promoting tubulin assembly and stabilizing microtubules, ultimately leading to cell death by apoptosis. It presents the ability to cross the blood brain barrier and has a much lower affinity for P-glycoprotein 1 than Docetaxel[1][2][3].
[1]. DiÉras V, et al. Phase II multicenter study of larotaxel (XRP9881), a novel taxoid, in patients with metastatic breast cancer who previously received taxane-based therapy. Ann Oncol. 2008 Jul;19(7):1255-60. [2]. Morris PG, et al. Novel anti-tubulin cytotoxic agents for breast cancer. Expert Rev Anticancer Ther. 2009 Feb;9(2):175-85. [3]. Zatloukal P, et al. Randomized multicenter phase II study of larotaxel (XRP9881) in combination with cisplatin or gemcitabine as first-line chemotherapy in nonirradiable stage IIIB or stage IV non-small cell lung cancer. J Thorac Oncol. 2008 Aug;3(8):894-901.
| Cas No. | 156294-36-9 | SDF | |
| 别名 | XRP9881 | ||
| Canonical SMILES | O=C([C@]1([H])OC(C)=O)[C@@]23[C@@]([C@@H]([C@@]4(O)C(C)(C)C1=C([C@H](OC([C@H](O)[C@H](C5=CC=CC=C5)NC(OC(C)(C)C)=O)=O)C4)C)OC(C6=CC=CC=C6)=O)([H])[C@]7([C@@](OC7)([H])C[C@@H]2C3)OC(C)=O | ||
| 分子式 | C45H53NO14 | 分子量 | 831.9 |
| 溶解度 | DMSO: ≥ 50 mg/mL (60.10 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 | 1.2021 mL | 6.0103 mL | 12.0207 mL |
| 5 mM | 0.2404 mL | 1.2021 mL | 2.4041 mL |
| 10 mM | 0.1202 mL | 0.601 mL | 1.2021 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。
Nanostructure of Functional Larotaxel Liposomes Decorated with Guanine-Rich Quadruplex Nucleotide-Lipid Derivative for Treatment of Resistant Breast Cancer
Small 2021 Apr;17(13):e2007391.PMID:33522108DOI:10.1002/smll.202007391.
Breast cancer is the most common malignant disease in women all over the world and its chemotherapy outcome is restricted by multidrug resistance. Here, a nanostructure by functional Larotaxel liposomes decorated with guanine-rich quadruplex nucleotide-lipid derivative for treatment of resistant breast cancer is developed. The studies are performed on the resistant breast cancer cells and the cancer-bearing mice. The nucleotide-lipid derivative (DSPE-PEG2000 -C6 -GT28nt) is synthesized by introducing a hydrophobic hexyl linkage between GT-28nt (containing 17 guanines and 11 thymidines) and DSPE-PEG2000 -NHS, and is incorporated on the functional Larotaxel liposomes for specific binding with nucleolin receptor on the resistant cancer cells. The studies demonstrate that the liposomes had long circulatory effect, targeted capability, and significant anticancer efficacy in resistant cancer-bearing mice. The studies further reveal their action mechanism, consisting of blocking depolymerization of microtubules, arresting cell cycle, blocking JAK-STAT signaling pathway, and inhibiting activity of antiapoptotic proteins. In conclusion, the functional Larotaxel liposomes can be used for effective treatment of drug-resistant breast cancer, and this study also offers a novel targeted nanomedicine based on nucleotide-lipid derivative.
Larotaxel: broadening the road with new taxanes
Expert Opin Investig Drugs 2009 Aug;18(8):1183-9.PMID:19604119DOI:10.1517/13543780903119167.
Significant advances in cancer treatment have been achieved with novel targeted and state-of-the-art treatments. While the targeted treatments have received much attention in recent years, the more 'traditional' chemotherapeutic agents continue to play an important role in several malignancies. Former taxanes such as docetaxel and paclitaxel, with their broad anticancer activity, have contributed significantly to the improved treatment of a number of neoplastic diseases. Unfortunately, until now, the achievements obtained with these compounds have been mitigated by clinical limitations such as acquired or intrinsic resistance of tumors, poor CNS activity, allergic reactions and unfavorable toxicity profiles. Larotaxel (RPR 109881A) is a taxane analogue with a broad spectrum of activity and different toxicity profile and with the possible advantages of surpassing some mechanisms of resistance and penetrating into the CNS. The development path of this drug, its core clinical data and future treatment perspectives are discussed in this article.
[Spectrometric analyses of Larotaxel and Larotaxel liposomes quantification by high performance liquid chromatography]
Beijing Da Xue Xue Bao Yi Xue Ban 2019 Jun 18;51(3):467-476.PMID:31209418DOI:10.19723/j.issn.1671-167X.2019.03.014.
Objective: Larotaxel is a new chemical structure drug, which has not been marketed worldwide. Accordingly, the standard identification and quantification methods for Larotaxel remain unclear. The spectrometric analyses were performed for verifying weight molecular formula, molecular weight and chemical structure of Larotaxel. Besides, a quantification method was developed for measuring Larotaxel in the liposomes. Methods: The molecular formula, molecular weight and chemical structure of Larotaxel were studied by using mass spectrometry (MS), infra-red (IR), nuclear magnetic resonance (NMR) and ultraviolet-visible (UV-vis) spectrometric techniques. The absorption wavelength of Larotaxel was investigated by UV-vis spectrophotometry full-wavelength scanning. Besides, a quantification method was developed by high performance liquid chromatography (HPLC), and then validated by measuring the encapsulation efficacy of Larotaxel liposomes. Results: The four spectral characteristics of Larotaxel were revealed and the corresponding standard spectra were defined. It was confirmed that Larotaxel had the structure of tricyclic diterpenoids, with the molecular formula of C45H53NO14, the molecular weight of 831.900 1, and the maximum absorption wavelength of 230 nm. The quantitative method of Larotaxel was established by using HPLC with a reversed phase C18 column (5 μm, 250 mm×4.6 mm), a mobile phase of acetonitrile-water (75:25, volume/volume), and a detection wavelength of 230 nm. The validation study exhibited that the established HPLC method was stable, and had a high recovery and precision in the quantitative measurement of Larotaxel in liposomes. In addition, a new kind of Larotaxel liposomes was also successfully prepared. The particle size of the liposomes was about 105 nm, with an even size distribution. And the encapsulation efficiency of Larotaxel in the liposomes was above 80%. Conclusion: The present study offers reference standard spectra of Larotaxel, including MS, IR, NMR, and UV-vis, and confirms the molecular formula, molecular weight and chemical structure of Larotaxel. Besides, the study develops a rapid HPLC method for quality control of Larotaxel liposomes.
Degradation kinetics of Larotaxel and identification of its degradation products in alkaline condition
J Pharm Anal 2017 Apr;7(2):118-122.PMID:29404026DOI:10.1016/j.jpha.2016.11.002.
Larotaxel, a new taxane compound prepared by partial synthesis from 10-deacetyl baccatin III, is active against tumors. In this research, a selective LC-MS method was developed and validated for the study of degradation kinetics of Larotaxel, which was carried out in aqueous solutions with different pH (1.5, 3.0, 5.0, 6.5, 7.4, 9.0, 10 and 11.0) and temperature (0, 25, 37 and 45 °C). The linear range was 0.5-25 μg/mL, the intra- and inter-day precisions were less than 7.0%, and accuracy ranged from 97.4-104.5% for each analyte. The observed rate obtained by measuring the remaining intact Larotaxel was shown to follow first-order kinetics. The activation energies for degradation were 126.7 and 87.01 kJ/mol at pH 1.5 and 11, respectively. Although Larotaxel was stable in pH 5, 6.5 and 7.4 buffers at 37 °C for 24 h during our study, increasing or decreasing the pH of the solutions would decrease its stabilities. Moreover, three main degradation products in alkaline condition were separated by HPLC and identified by Q-TOF-MS. The three degradation products were confirmed as 10-deacetyl Larotaxel, 7, 8-cyclopropyl baccatin Ⅲ and 10-deacetyl-7, 8-cyclopropyl baccatin Ⅲ.
Larotaxel with Cisplatin in the first-line treatment of locally advanced/metastatic urothelial tract or bladder cancer: a randomized, active-controlled, phase III trial (CILAB)
Oncology 2013;85(4):208-15.PMID:24080920DOI:10.1159/000354085.
Background: This open-label, randomized phase III trial evaluated Larotaxel/cisplatin versus gemcitabine/cisplatin as first-line treatment for locally advanced (T4b) or metastatic urothelial tract or bladder cancer. Methods: Patients were randomized to Larotaxel 50 mg/m(2) with cisplatin 75 mg/m(2) every 3 weeks (Larotaxel/cisplatin) or gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 with cisplatin 70 mg/m(2) on day 1 every 4 weeks (gemcitabine/cisplatin). The primary endpoint was overall survival (OS). Results: The trial was prematurely closed following the sponsor's decision to stop clinical development of Larotaxel (n = 337 randomized). The Larotaxel dose was reduced to 40 mg/m(2) and cisplatin to 60 mg/m(2) following a data monitoring committee safety review of the first 97 patients. At the time of analysis, the median OS was 13.7 months [95% confidence interval (CI) 11.2-17.1] with Larotaxel/cisplatin and 14.3 months (95% CI 10.5 to not reached) with gemcitabine/cisplatin [hazard ratio (HR) 1.21; 95% CI 0.83-1.76; p = 0.33]. The median progression-free survival (PFS) was 5.6 months (95% CI 4.1-6.2) with Larotaxel/cisplatin and 7.6 months (95% CI 6.6-9.1) with gemcitabine/cisplatin (HR 1.67; 95% CI 1.24-2.25). More myelosuppression was observed with gemcitabine/cisplatin. Conclusion: There was no difference in OS. Although the trial was closed prematurely, PFS appeared worse with Larotaxel/cisplatin, suggesting that Larotaxel/cisplatin does not improve outcomes versus cisplatin/gemcitabine.