LTX-401
目录号 : GC31860
LTX-401是一种可靶向作用高尔基体(Golgiapparatus)的溶瘤氨基酸衍生物。
Cas No.:1398051-86-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | The MTT assay is employed to investigate the in vitro cytotoxicity of LTX-401 against a selection of both cancer and non-malignant cell lines. Pre-cultured cells are seeded at a density between 1x104-1.5x104 cells/well. The cytotoxic activity of LTX-401 against human red blood cells (RBCs) is determined by a hemolytic assay using freshly isolated blood from healthy individuals who gave their signed informed consent. RBCs are resuspended to a 10% hematocrit solution before being incubated for 1 h at 37°C with LTX-401 dissolved in PBS at concentrations ranging from 136-1358 μM (50-500 μg/mL). RBCs with PBS and 1% Triton solution alone serves as a negative and positive control, respectively. After centrifuging the samples at 4,000 rpm for 5 minutes, the absorbance of the supernatant is measured at 405 nm on a spectrophotometric microliter plate reader[1]. |
Animal experiment: | Mice[1]Female C57BL/6 wild-type mice, 5-6 weeks old, are used. All animals are housed in the same room and in cages (containing 2-5 mice) specially designed for mice, with a 12 h/12 h day-night cycle, and allowed ad libitum access to high quality food and water. Animals are weighed weekly and monitored several times per week, and no unexpected deaths are observed. B16F1 cells are harvested, washed in serum-free RPMI and injected intradermally (i.d) into the right side of the abdomen in C57BL/6 mice (7.5x104 B16F1 cells per mouse/50 μL RPMI-1640). Palpable tumors (20-30 mm2) are injected intratumorally (i.t) with either LTX-401 (5 mg/mL) or a vehicle (saline) once per day for three consecutive days. Animals are euthanized according to humane endpoints such as a weight loss of >10%, general physical discomfort or reduced activity, severe tumor necrosis or ulceration, or if the tumor size exceeds 130 mm2. All animals are euthanized using cervical dislocation[1]. |
References: [1]. Liv-Marie Eike, et al. The Cytolytic Amphipathic β(2,2)-Amino Acid LTX-401 Induces DAMP Release in Melanoma Cells and Causes Complete Regression of B16 Melanoma. PLoS One. 2016; 11(2): e0148980. | |
LTX-401, an oncolytic amino acid derivative, targets the Golgi apparatus.
LTX-401, an oncolytic amino acid derivative, targets the Golgi apparatus[2]. LTX-401 effectively reduces the viability of several tumor cell lines in vitro, with a similar degree of cytotoxicity against non-malignant cell lines such as HUV-EC-C endothelial cells, HaCat keratinocytes and MRC-5 fibroblasts. LTX-401 displays the highest cytotoxic activity against the human malignant melanoma cell line MDA-MB-435S (13.5 μM), and is least active against the human hepatocellular carcinoma cell line HEPG2 (35.4 μM). For the remaining cell lines, LTX-401 exhibits similar IC50 values, varying slightly within the range of 19-32 μM. No in vitro hemolytic activity against RBCs is observed using the same concentrations required for the induction of cell death in cancer cell lines. A 50% hemolysis is observed using higher concentrations of LTX-401 (400 μg/mL=1087 μM)[1].
The majority (9/11) of the animals demonstrate a complete and lasting tumor regression after intratumoral treatment with LTX-401. Samples are collected from selected animals in the treatment group and control group on days 2 and 7 post-treatment with a single i.t injection. The immunolabelling of tumor tissue with anti-CD3 antibody reveals that a majority of the infiltrating cells are CD3+ T cells, whereas tumors injected with vehicle only exhibit tumors with a viable tumor tissue, with minimal necrosis and few lymphocytes[1].
[1]. Liv-Marie Eike, et al. The Cytolytic Amphipathic β(2,2)-Amino Acid LTX-401 Induces DAMP Release in Melanoma Cells and Causes Complete Regression of B16 Melanoma. PLoS One. 2016; 11(2): e0148980. [2]. Heng Zhou, et al. The oncolytic compound LTX-401 targets the Golgi apparatus. Cell Death Differ. 2018 Jan; 25(1): 227-228.
| Cas No. | 1398051-86-9 | SDF | |
| Canonical SMILES | [NH3+]CC(CCCC1=CC=CC=C1)(C(NCC[NH3+])=O)CCCC2=CC=CC=C2 | ||
| 分子式 | C23H35N3O | 分子量 | 369.54 |
| 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 | 2.7061 mL | 13.5303 mL | 27.0607 mL |
| 5 mM | 0.5412 mL | 2.7061 mL | 5.4121 mL |
| 10 mM | 0.2706 mL | 1.353 mL | 2.7061 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。
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Tumor lysis with LTX-401 creates anticancer immunity
Local immunotherapies such as the intratumoral injection of oncolytic compounds aim at reinstating and enhancing systemic anticancer immune responses. LTX-315 is a first-in-class, clinically evaluated oncolytic peptide-based local immunotherapy that meets these criteria. Here, we show that LTX-401, yet another oncolytic compound designed for local immunotherapy, depicts a similar safety profile and that sequential local inoculation of LTX-401 was able to cure immunocompetent host from subcutaneous MCA205 and TC-1 cancers. Cured animals exhibited long-term immune memory effects that rendered them resistant to rechallenge with syngeneic tumors. Nevertheless, the local treatment with LTX-401 alone had only limited abscopal effects on secondary contralateral lesions. Anticancer effects resulting from single as well as sequential injections of LTX-401 were boosted in combination with PD-1 and CTLA-4 immune checkpoint blockade (ICB), and sequential LTX-401 treatment combined with double ICB exhibited strong abscopal antineoplastic effects on contralateral tumors underlining the potency of this combination therapy.
The oncolytic compound LTX-401 targets the Golgi apparatus
LTX-401 is an oncolytic amino acid derivative with potential immunogenic properties. Here, we demonstrate that LTX-401 selectively destroys the structure of the Golgi apparatus, as determined by means of ultrastructural analyses and fluorescence microscopic observation of cells expressing Golgi-targeted GFP reporters. Subcellular fractionation followed by mass spectrometric detection revealed that LTX-401 selectively enriched in the Golgi rather than in mitochondria or in the cytosol. The Golgi-dissociating agent Brefeldin A (BFA) reduced cell killing by LTX-401 as it partially inhibited LTX-401-induced mitochondrial release of cytochrome c and the activation of BAX. The cytotoxic effect of LTX-401 was attenuated by the double knockout of BAX and BAK, as well as the mitophagy-enforced depletion of mitochondria, yet was refractory to caspase inhibition. LTX-401 induced all major hallmarks of immunogenic cell death detectable with biosensor cell lines including calreticulin exposure, ATP release, HMGB1 exodus and a type-1 interferon response. Moreover, LTX-401-treated tumors manifested a strong lymphoid infiltration. Altogether these results support the contention that LTX-401 can stimulate immunogenic cell death through a pathway in which Golgi-localized LTX-401 operates upstream of mitochondrial membrane permeabilization.
The Novel Oncolytic Compound LTX-401 Induces Antitumor Immune Responses in Experimental Hepatocellular Carcinoma
LTX-401 is a novel oncolytic compound designed for the local treatment of solid tumors. In the present study, we have examined the applicability and efficacy of LTX-401 in a rat model JM1 hepatocellular carcinoma, with particular interest in its ability to induce antitumor immunity. LTX-401 induces necrotic cell death followed by the release of immunogenic cell death mediators such as high-mobility group box 1 protein, ATP, and cytochrome c. When injected into subcutaneous and orthotopic JM1 tumors, LTX-401 treatment resulted in a strong antitumoral effect followed by complete tumor regression in the majority of animals. Additionally, LTX-401 could affect the growth of distal tumor deposits simulating metastases, hence indicating immune-mediated abscopal responses. Furthermore, LTX-401 treatment induced tumor-specific immune responses as seen by protection against tumor rechallenge and increased production of interferon-gamma (IFN-γ) by splenic cells in response to stimulation with tumor cells. Taken together, our data demonstrate that the oncolytic compound LTX-401 provides local tumor control followed by protective immune responses and may be exploited as a novel immunotherapeutic agent in hepatocellular carcinoma.
The oncolytic compound LTX-401 targets the Golgi apparatus
This corrects the article DOI: 10.1038/cdd.2016.86.
The Cytolytic Amphipathic β(2,2)-Amino Acid LTX-401 Induces DAMP Release in Melanoma Cells and Causes Complete Regression of B16 Melanoma
In the present study we examined the ability of the amino acid derivative LTX-401 to induce cell death in cancer cell lines, as well as the capacity to induce regression in a murine melanoma model. Mode of action studies in vitro revealed lytic cell death and release of danger-associated molecular pattern molecules, preceded by massive cytoplasmic vacuolization and compromised lysosomes in treated cells. The use of a murine melanoma model demonstrated that the majority of animals treated with intratumoural injections of LTX-401 showed complete and long-lasting remission. Taken together, these results demonstrate the potential of LTX-401 as an immunotherapeutic agent for the treatment of solid tumors.