Chlorotoxin
(Synonyms: 氯毒素) 目录号 : GC33024
Chlorotoxin是从雷蛇属以色列蝎子的毒液中提取的由36个氨基酸组成的肽段，具有抗癌活性。Chlorotoxin是氯离子通道(chloridechannel)阻断剂。
Cas No.:163515-35-3
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
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Animal experiment: |
Mouse: At 24, 48, 72, and 96 h after tumor-bearing and control SCID mice are injected with 125l-labeled Chlorotoxin, they are anesthetized and imaged. Both 125I- and 131l-labeled Chlorotoxin-injected animals and their control counterparts are killed at indicated time points for biodistribution studies[3]. |
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References: [1]. DeBin JA, et al. Purification and characterization of chlorotoxin, a chloride channel ligand from the venom of the scorpion. Am J Physiol. 1993 Feb;264(2 Pt 1):C361-9. |
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Chlorotoxin is a 36 amino-acid peptide from the venom of the Israeli scorpion Leiurus quinquestriatus with anticancer activity. Chlorotoxin is a chloride channel blocker.
Chlorotoxin (Chlorotoxin) preferentially binds to tumor cells and has been harnessed to develop an imaging agent to help visualize tumors during surgical resection. In addition, chlorotoxin has potential as a vehicle to deliver anti-cancer drugs specifically to cancer cells. Chlorotoxin is shown to bind glioma cells, but is unable to bind normal rat astrocytes and Te671, a human rhabdomyosarcoma cell line. Chlorotoxin inhibits the migration of U251MG (glioma) cells, with an IC50 of 600 nM[2]. Chlorotoxin binds to glioma cells is specific and involves high affinity (Kd=4.2 nM) and low affinity (Kd=660 nM) binding sites[3].Small conductance chloride channels are shown to be potently blocked by Chlorotoxin. Chlorotoxin has been used as a general pharmacological tool to investigate the function of chloride channels[4].
Chlorotoxin shows insecticidal activity on insects and other invertebrates. After the administration of I-Chlorotoxin to tumor-bearing mice, the peptides accumulated within the tumor[2].Chlorotoxin selectively accumulates in the brain of tumor-bearing mice with calculated brain: muscle ratios of 36.4% of injected dose/g (ID/g), as compared to 12.4%ID/g in control animals[3].
[1]. DeBin JA, et al. Purification and characterization of chlorotoxin, a chloride channel ligand from the venom of the scorpion. Am J Physiol. 1993 Feb;264(2 Pt 1):C361-9. [2]. Ojeda PG, et al. Chlorotoxin: Structure, activity, and potential uses in cancer therapy. Biopolymers. 2016 Jan;106(1):25-36. [3]. Soroceanu L, et al. Use of chlorotoxin for targeting of primary brain tumors. Cancer Res. 1998 Nov 1;58(21):4871-9. [4]. Dardevet L, et al. Chlorotoxin: a helpful natural scorpion peptide to diagnose glioma and fight tumor invasion. Toxins (Basel). 2015 Mar 27;7(4):1079-101.
| Cas No. | 163515-35-3 | SDF | |
| 别名 | 氯毒素 | ||
| Canonical SMILES | Met-Cys-Met-Pro-Cys-Phe-Thr-Thr-Asp-His-Gln-Met-Ala-Arg-Lys-Cys-Asp-Asp-Cys-Cys-Gly-Gly-Lys-Gly-Arg-Gly-Lys-Cys-Tyr-Gly-Pro-Gln-Cys-Leu-Cys-Arg-NH2 (Disulfide bridge: Cys2-Cys19,Cys5-Cys28,Cys16-Cys33,Cys20-Cys35) | ||
| 分子式 | C158H249N53O47S11 | 分子量 | 3995.71 |
| 溶解度 | Soluble in DMSO | 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 | 0.2503 mL | 1.2513 mL | 2.5027 mL |
| 5 mM | 0.0501 mL | 0.2503 mL | 0.5005 mL |
| 10 mM | 0.025 mL | 0.1251 mL | 0.2503 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。
Chlorotoxin-directed CAR T cells for specific and effective targeting of glioblastoma
Sci Transl Med 2020 Mar 4;12(533):eaaw2672.PMID:32132216DOI:10.1126/scitranslmed.aaw2672.
Although chimeric antigen receptor (CAR) T cells have demonstrated signs of antitumor activity against glioblastoma (GBM), tumor heterogeneity remains a critical challenge. To achieve broader and more effective GBM targeting, we developed a peptide-bearing CAR exploiting the GBM-binding potential of Chlorotoxin (CLTX). We find that CLTX peptide binds a great proportion of tumors and constituent tumor cells. CAR T cells using CLTX as the targeting domain (CLTX-CAR T cells) mediate potent anti-GBM activity and efficiently target tumors lacking expression of other GBM-associated antigens. Treatment with CLTX-CAR T cells resulted in tumor regression in orthotopic xenograft GBM tumor models. CLTX-CAR T cells do not exhibit observable off-target effector activity against normal cells or after adoptive transfer into mice. Effective targeting by CLTX-CAR T cells requires cell surface expression of matrix metalloproteinase-2. Our results pioneer a peptide toxin in CAR design, expanding the repertoire of tumor-selective CAR T cells with the potential to reduce antigen escape.
Chlorotoxin: a helpful natural scorpion peptide to diagnose glioma and fight tumor invasion
Toxins (Basel) 2015 Mar 27;7(4):1079-101.PMID:25826056DOI:10.3390/toxins7041079.
Chlorotoxin is a small 36 amino-acid peptide identified from the venom of the scorpion Leiurus quinquestriatus. Initially, Chlorotoxin was used as a pharmacological tool to characterize chloride channels. While studying glioma-specific chloride currents, it was soon discovered that Chlorotoxin possesses targeting properties towards cancer cells including glioma, melanoma, small cell lung carcinoma, neuroblastoma and medulloblastoma. The investigation of the mechanism of action of Chlorotoxin has been challenging because its cell surface receptor target remains under questioning since two other receptors have been claimed besides chloride channels. Efforts on chlorotoxin-based applications focused on producing analogues helpful for glioma diagnosis, imaging and treatment. These efforts are welcome since gliomas are very aggressive brain cancers, close to impossible to cure with the current therapeutic arsenal. Among all the chlorotoxin-based strategies, the most promising one to enhance patient mean survival time appears to be the use of Chlorotoxin as a targeting agent for the delivery of anti-tumor agents. Finally, the discovery of Chlorotoxin has led to the screening of other scorpion venoms to identify chlorotoxin-like peptides. So far several new candidates have been identified. Only detailed research and clinical investigations will tell us if they share the same anti-tumor potential as Chlorotoxin.
Chlorotoxin: Structure, activity, and potential uses in cancer therapy
Biopolymers 2016 Jan;106(1):25-36.PMID:26418522DOI:10.1002/bip.22748.
Chlorotoxin is a disulfide-rich stable peptide from the venom of the Israeli scorpion Leiurus quinquestriatus, which has potential therapeutic applications in the treatment of cancer. Its ability to preferentially bind to tumor cells has been harnessed to develop an imaging agent to help visualize tumors during surgical resection. In addition, Chlorotoxin has attracted interest as a vehicle to deliver anti-cancer drugs specifically to cancer cells. Given its interesting structural and biological properties, Chlorotoxin also has the potential to be used in a variety of other biotechnology and biomedical applications. Here, we review the structure, activity and potential applications of Chlorotoxin as a drug design scaffold.
Chlorotoxin-A Multimodal Imaging Platform for Targeting Glioma Tumors
Toxins (Basel) 2018 Nov 26;10(12):496.PMID:30486274DOI:10.3390/toxins10120496.
Chlorotoxin (CTX) is a 36-amino-acid disulfide-containing peptide derived from the venom of the scorpion Leiurus quinquestriatus. CTX alters physiology in numerous ways. It interacts with voltage gated chloride channels, Annexin-2, and matrix metalloproteinase-2 (MMP-2). CTX-based bioconjugates have been widely subjected to phase I/II clinical trials and have shown substantial promise. Many studies have demonstrated that CTX preferentially binds to neuroectodermal tumors, such as glioblastoma, without cross-reactivity to normal brain cells. With its ability to penetrate the blood-brain-barrier (BBB) and its tyrosine residue allows covalent conjugation with functional moieties, CTX is an attractive platform to explore development of diagnostic and therapeutic agents for gliomas. In this review, we outline CTX structure and its molecular targets, summarize molecular variations of CTX developed for glioma imaging, and discuss future trends and perspectives for CTX conjugates as a theranostic agent.
Glioblastoma multiforme targeted therapy: The Chlorotoxin story
J Clin Neurosci 2016 Nov;33:52-58.PMID:27452128DOI:10.1016/j.jocn.2016.04.012.
Glioblastoma multiforme (GBM) is the most common malignant primary brain neoplasm having a mean survival of <24months. Scorpion toxins are considered promising cancer drug candidates, primarily due to the discovery of hlorotoxin, derived from the venom of the Israeli yellow scorpion. This intriguing short peptide of only 36 amino-acids length and tight configuration, possess the ability to bind to GBM cells in a grade-related manner with ∼100% of GBM cells staining positive and no cross reactivity to normal brain. Chlorotoxin has an anti-angiogenic effect as well. Molecular targets for Chlorotoxin include voltage gated chloride channels (GCC), calcium-dependent phospholipid-binding protein Annexin-2, and the inducible extracellular enzyme Matrix Metalloproteinase-2 (MMP-2). Of all its targets, MMP-2 seems to bear the most anti-neoplastic potential. Chlorotoxin is a promising tumortargeting peptide. Its small size and compact shape are convenient for intracranial delivery. We present a short discussion on Chlorotoxin. The structure, biological activity, molecular targets and possible clinical role of Chlorotoxin are discussed. Chlorotoxin can be utilized as a targeting domain as well, attaching different effector functions to it. Clinical applications in GBM therapy, intraoperative imaging, nano-probes and nano-vectors based technology; targeted chemotherapy and immunotherapy are discussed as well. Chlorotoxin is likely to play a significant role in effective GBM immunotherapy in the future.