Squalamine lactate (MSI-1256F)
(Synonyms: MSI-1256F) 目录号 : GC32161
乳酸角鲨胺 (MSI-1256F) 是一种在角鲨组织中发现的氨基甾醇化合物，具有抗菌活性，用于治疗新生血管性年龄相关性黄斑变性。
Cas No.:320725-47-1
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
Squalamine lactate is an aminosterol compound discovered in the tissues of the dogfish shark, with antimicrobial activity, and used for the treatment of neovascular age-related macular degeneration.
Squalamine lactate has a more generalized effect on the cellular signaling cascade that is common to both VEGF and other growth factors[1]. Squalamine blocks the action of VEGF and integrin expression, thereby inhibiting angiogenesis, when bound to calmodulin[2].
Squalamine is ineffective when administered intravitreally and therefore requires intravenous dosing. However, systemic dosing has yielded promising results in rats as well as humans[2].
[1]. Hussain RM, et al. Emerging vascular endothelial growth factor antagonists to treat neovascular age-related macular degeneration. Expert Opin Emerg Drugs. 2017 Sep;22(3):235-246. [2]. Emerson MV, et al. Current and emerging therapies for the treatment of age-related macular degeneration. Clin Ophthalmol. 2008 Jun;2(2):377-88.
| Cas No. | 320725-47-1 | SDF | |
| 别名 | MSI-1256F | ||
| Canonical SMILES | NCCCCNCCCN[C@H]1CC[C@@]2(C)[C@](C[C@@H](O)[C@]3([H])[C@]2([H])CC[C@@]4(C)[C@@]3([H])CC[C@]4([H])[C@H](C)CC[C@@H](OS(=O)(O)=O)C(C)C)([H])C1.C[C@@H](C(O)=O)O | ||
| 分子式 | C37H71N3O8S | 分子量 | 718.04 |
| 溶解度 | DMSO : ≥ 36.66 mg/mL (51.06 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.3927 mL | 6.9634 mL | 13.9268 mL |
| 5 mM | 0.2785 mL | 1.3927 mL | 2.7854 mL |
| 10 mM | 0.1393 mL | 0.6963 mL | 1.3927 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。
Innovative therapies for neovascular age-related macular degeneration
Expert Opin Pharmacother 2019 Oct;20(15):1879-1891.PMID:31298960DOI:10.1080/14656566.2019.1636031.
Introduction: Investigational anti-VEGF treatments for neovascular age-related macular degeneration (nAMD) aim to improve visual outcomes and reduce treatment burden; these include long-acting agents, combination strategies, topical agents, sustained-release, and genetic therapies. Areas covered: The authors provide a comprehensive review of investigational therapies for nAMD, focusing on therapies currently in clinical trial. Expert opinion: Long-acting anti-VEGF agents have demonstrated promising results in phase 3 studies, and include Brolucizumab, a single-chain antibody fragment, and Abicipar, a designed ankyrin repeat protein (DARPin). Other unique anti-VEGF agents in current trials include Conbercept - a fusion protein of the VEGF receptor domains, KSI-301 - an anti-VEGF antibody biopolymer conjugate, and OPT-302 - an inhibitor of VEGF-C/D. Strategies to activate the Tie-2 receptor, some in combination with VEGF inhibition, are of interest, with recent trials of Faricimab, ARP-1536, and nesvacumab. Topical anti-VEGF ± anti-PDGF agents, such as pazopanib, Squalamine lactate, regorafenib, and LHA510 have shown limited efficacy and/or have not been advanced, although PAN-90806 continues to advance with promising initial results. Sustained-release anti-VEGF treatments, to address treatment burden, include the ranibizumab Port Delivery System, GB-102, NT-503, hydrogel depot, Durasert, and ENV1305. Similarly, genetic therapies, including RGX-314 and ADVM-022, aim to provide sustained anti-VEGF expression from the retina.
Squalamine lactate for exudative age-related macular degeneration
Ophthalmol Clin North Am 2006 Sep;19(3):381-91, vi.PMID:16935213DOI:10.1016/j.ohc.2006.05.003.
Squalamine lactate inhibits angiogenesis by a long-lived, intracellular mechanism of action. The drug is taken up into activated endothelial cells through caveolae, small invaginations in the cellular membrane. Subsequently, the drug binds to and "chaperones" calmodulin to an intracellular membrane compartment and blocks angiogenesis at several levels. A series of basic investigations, preclinical studies, and human clinical trials have begun to establish the proof of concept, efficacy, and safety parameters for use of Squalamine lactate as a therapeutic agent for exudative age-related macular degeneration and several types of malignancies.
Squalamine lactate reduces choroidal neovascularization in a laser-injury model in the rat
Retina 2003 Dec;23(6):808-14.PMID:14707832DOI:10.1097/00006982-200312000-00011.
Purpose: To determine if systemically administered Squalamine lactate, a novel aminosterol with antineoplastic and antiangiogenic activity, inhibits the development of experimental choroidal neovascularization membranes (CNVMs) induced by laser trauma in a rat model. Methods: Twenty anesthetized male Brown-Norway rats received a series of 8 krypton red laser lesions per eye (647 nm, 0.05 second, 50 microm, 150 mW). One half the animals received an intraperitoneal injection of squalamine and the other one half received an injection of 5% dextrose in water, all performed in a masked fashion. Fundus photography and fluorescein angiography were performed at postlaser treatment days 14 and 28, and ocular tissues were processed for light microscopic examination following euthanasia of the rats on postlaser treatment day 28. Results: Although fundus photography and fluorescein angiography yielded no statistically significant quantitative differences between the two groups, histologic analysis of the lesion sites revealed a partial but statistically significant reduction of experimental CNVM development in the squalamine-treated population. In particular, the squalamine-treated eyes (n = 20) demonstrated lesions (n = 149) with a mean CNVM thickness +/- SD of 47 +/- 11 microm, as compared with the control eyes (n = 20) that had lesions (n = 142) with a mean CNVM thickness +/- SD of 63 +/- 14 microm (P < 0.001). Conclusion: Systemically administered Squalamine lactate partially reduced choroidal neovascular membrane development induced by laser trauma in this animal model. In conjunction with other existing and developing therapies, this agent may have a potential role in the treatment of human CNVM formation. Further study of Squalamine lactate for treatment of neovascular eye disease is warranted.
A phase I/IIA trial of continuous five-day infusion of Squalamine lactate (MSI-1256F) plus carboplatin and paclitaxel in patients with advanced non-small cell lung cancer
Clin Cancer Res 2003 Sep 15;9(11):4108-15.PMID:14519633doi
Purpose: Squalamine is an antitumor agent that has been shown to have antiangiogenic activity in animal models. This Phase I/IIA study was designed to assess the safety, clinical response, and pharmacokinetics of squalamine when administered as a 5-day continuous infusion in conjunction with standard chemotherapy every 3 weeks in patients with stage IIIB (pleural effusion) or stage IV non-small cell lung cancer. Experimental design: Patients with chemotherapy-naive non-small cell lung cancer were treated with escalating doses of squalamine in combination with standard doses of paclitaxel and carboplatin. Paclitaxel and carboplatin were administered on day 1, followed by squalamine as a continuous infusion on days 1-5, every 21 days. Results: A total of 45 patients were enrolled (18 patients in the Phase I dose escalation arm and 27 in the Phase IIA arm). The starting dose of squalamine was 100 mg/m(2)/day and escalated to 400 mg/m(2)/day; two of three patients at 400 mg/m(2)/day had dose-limiting toxicity that included grade 3/4 arthralgia, myalgia, and neutropenia. On the basis of safety and toxicity, 300 mg/m(2)/day was selected as the Phase II dose of squalamine in this combination regimen. An additional 27 patients (a total of 33) were enrolled according to the protocol treatment schema at 300 mg/m(2)/day. There was no pharmacokinetic evidence of drug interactions for the combination of squalamine, carboplatin, and paclitaxel. Forty-three patients were evaluable for response. Partial tumor responses were observed in 12 (28%) of these patients; an additional 8 evaluable patients (19%) were reported to have stable disease. For all of the patients treated, the median survival was 10.0 months; and 1-year survival was 40%. Conclusions: The combination of squalamine given continuously daily for 5 days, with paclitaxel and carboplatin given on day 1, is well tolerated. Patient survival data and the safety profile of this drug combination suggests that the use of squalamine given at its maximum tolerated dose with cytotoxic chemotherapy should be explored further as a potentially effective therapeutic strategy for patients with stage IIIB or IV non-small cell lung cancer.
Determination of degradation products of Squalamine lactate using LC/MS
J Pharm Biomed Anal 2003 Apr 24;32(1):85-96.PMID:12852451DOI:10.1016/s0731-7085(03)00047-5.
Heat, acid and base stress methods were applied to study the stability of Squalamine lactate. Liquid chromatography coupled with mass spectrometry was used to analyze the degraded samples and tentative structural identifications were assigned based on their molecular weight measurements, reactivity and MS/MS fragmentation. Solid Squalamine lactate generated a new amide, namely lactyl squalamide, when heated to 80 degrees C. Chemical structure for this new compound has been established by NMR and MS data interpretation and confirmed by direct comparison between the degradant and the synthesized compound. Squalamine lactate in pH 4 acetate buffer solution produced more degradants under stressed conditions. These degradants are formed due to the loss of the sulfate functionality. Squalamine lactate is stable in refrigerated conditions as well as in basic solution.