Home>>LTX-315 (K-K-W-W-K-K-W-Dip-K-NH2)

LTX-315 (K-K-W-W-K-K-W-Dip-K-NH2) Sale

目录号 : GC32894

Ruxotemitide (LTX 315, Oncopore) is the oncolytic peptide that kills cancer cells through Bax/Bak-regulated mitochondrial membrane permeabilization.

LTX-315 (K-K-W-W-K-K-W-Dip-K-NH2) Chemical Structure

Cas No.:1345407-05-7

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2mg
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¥1,339.00
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10mg
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¥4,284.00
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50mg
¥8,211.00
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Sample solution is provided at 25 µL, 10mM.

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实验参考方法

Cell experiment:

Tumor cells are incubated for 4 hours with 10 concentrations of LTX-315 in 1/4 dilution step with a top dose of 400 µM, with 1% (final concentration) Triton X-100 as positive control and FBS-free culture medium as negative control. Cell cytotoxicity is measured using the MTS assay[1].

Animal experiment:

Mice: Tumor cells are harvested, ished in RPMI-1640 and injected intradermally (i.d.) into the right side of the abdomen in C57BL/6 mice. Palpable tumors are injected i.t. with single doses of LTX-315 or LTX-328 dissolved in saline (1.0 mg peptide/50 μL saline) once a day for 3 consecutive days, and the vehicle control is saline only (0.9% NaCl in sterile water). Tumor size is measured using an electronic caliper[2].

References:

[1]. Haug BE, et al. Discovery of a 9-mer Cationic Peptide (LTX-315) as a Potential First in Class Oncolytic Peptide. J Med Chem. 2016 Apr 14;59(7):2918-27.
[2]. Camilio KA, et al. Complete regression and systemic protective immune responses obtained in B16 melanomas after treatment with LTX-315. Cancer Immunol Immunother. 2014 Jun;63(6):601-13.

产品描述

Ruxotemitide (LTX 315, Oncopore) is the oncolytic peptide that kills cancer cells through Bax/Bak-regulated mitochondrial membrane permeabilization.

LTX-315 is highly active against both murine and human melanoma cell lines in vitro. while displaying low EC50 cytotoxic activity against human red blood cells. LTX-315 has been shown to induce the release of ATP and HMGB1 in vitro, both being DAMPs involved in ICD[1].

when syngeneic B16 melanomas are treated intralesionally, a majority of the animals (~80%) treated with LTX-315 experience a complete and long-lasting tumor regression. LTX-315 injection induces an extensive hemorrhagic necrosis of the tumor parenchyma and a massive infiltration of CD3+ T cells, indicating that the peptide induces a type of cell death that leads to an increase in the number of tumor-infiltrating lymphocytes (TILs). treatment of a single tumor with LTX-315 generates a systemic anti-tumor immune response that eradicated distant lesions and prevented reoccurrence following tumor rechallenge[1].

[1] Camilio KA ,et al. Oncoimmunology. 2014, 3: e29181. [2] Paal Brunsvig, et al. J Clin Oncol.2014, 32:5s.

Chemical Properties

Cas No. 1345407-05-7 SDF
Canonical SMILES Lys-Lys-Trp-Trp-Lys-Lys-Trp-Dip-Lys-NH2
分子式 C78H106N18O9 分子量 1439.79
溶解度 DMSO : ≥ 50 mg/mL (34.73 mM) 储存条件 Store at -20°C
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1 mM 0.6945 mL 3.4727 mL 6.9455 mL
5 mM 0.1389 mL 0.6945 mL 1.3891 mL
10 mM 0.0695 mL 0.3473 mL 0.6945 mL
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Research Update

Antimicrobial Peptides as Anticancer Agents: Functional Properties and Biological Activities

Molecules 2020 Jun 19;25(12):2850.PMID:32575664DOI:10.3390/molecules25122850.

Antimicrobial peptides (AMPs), or host defense peptides, are small cationic or amphipathic molecules produced by prokaryotic and eukaryotic organisms that play a key role in the innate immune defense against viruses, bacteria and fungi. AMPs have either antimicrobial or anticancer activities. Indeed, cationic AMPs are able to disrupt microbial cell membranes by interacting with negatively charged phospholipids. Moreover, several peptides are capable to trigger cytotoxicity of human cancer cells by binding to negatively charged phosphatidylserine moieties which are selectively exposed on the outer surface of cancer cell plasma membranes. In addition, some AMPs, such as LTX-315, have shown to induce release of tumor antigens and potent damage associated molecular patterns by causing alterations in the intracellular organelles of cancer cells. Given the recognized medical need of novel anticancer drugs, AMPs could represent a potential source of effective therapeutic agents, either alone or in combination with other small molecules, in oncology. In this review we summarize and describe the properties and the mode of action of AMPs as well as the strategies to increase their selectivity toward specific cancer cells.

Oncolytic peptide LTX-315 induces anti-pancreatic cancer immunity by targeting the ATP11B-PD-L1 axis

J Immunother Cancer 2022 Mar;10(3):e004129.PMID:35288467DOI:10.1136/jitc-2021-004129.

Background: LTX-315 is an oncolytic peptide deriving from bovine lactoferrin, with the ability to induce cancer immunogenic cell death. However, the mechanism used by LTX-315 to trigger the antitumor immune response is still poorly understood. The expression of programmed cell death ligand 1 (PD-L1) largely determines the efficacy and effectiveness of cancer immunotherapies targeting this specific immune checkpoint. This study aimed to demonstrate the potential effect and mechanism of LTX-315 in PD-L1 inhibition-induced anti-pancreatic cancer immunity. Methods: Both immunodeficient and immunocompetent mouse models were used to evaluate the therapeutic efficacy of monotherapy and combination therapy. Flow cytometry and immunohistochemistry were used to assess the immune microenvironment. Multiomic analysis was used to identify the potential target and down-streaming signaling pathway. Both in-house tissue microarray and open accessed The Cancer Genome Atlas data sets were used to evaluate the clinical relevance in pancreatic cancer prognosis. Results: LTX-315 treatment inhibited PD-L1 expression and enhanced lymphocyte infiltration in pancreatic tumors. ATP11B was identified as a potential target of LTX-315 and a critical regulator in maintaining PD-L1 expression in pancreatic cancer cells. As regards the mechanism, ATP11B interacted with PD-L1 in a CKLF-like MARVEL transmembrane domain containing 6 (CMTM6)-dependent manner. The depletion of ATP11B promoted CMTM6-mediated lysosomal degradation of PD-L1, thus reactivating the immune microenvironment and inducing an antitumor immune response. The significant correlation among ATP11B, CMTM6, and PD-L1 was confirmed in clinical samples of pancreatic cancer. Conclusions: LTX-315 was first identified as a peptide drug inducing PD-L1 downregulation via ATP11B. Therefore, LTX-315, or the development of ATP11B-targeting drugs, might improve the efficacy of cancer immunotherapy.

The oncolytic peptide LTX-315 triggers necrotic cell death

Cell Cycle 2015;14(21):3506-12.PMID:26566869DOI:10.1080/15384101.2015.1093710.

The oncolytic peptide LTX-315 has been designed for killing human cancer cells and turned out to stimulate anti-cancer immune responses when locally injected into tumors established in immunocompetent mice. Here, we investigated the question whether LTX-315 induces apoptosis or necrosis. Transmission electron microscopy or morphometric analysis of chromatin-stained tumor cells revealed that LTX-315 failed to induce apoptotic nuclear condensation and rather induced a necrotic phenotype. Accordingly, LTX-315 failed to stimulate the activation of caspase-3, and inhibition of caspases by means of Z-VAD-fmk was unable to reduce cell killing by LTX-315. In addition, 2 prominent inhibitors of regulated necrosis (necroptosis), namely, necrostatin-1 and cycosporin A, failed to reduce LTX-315-induced cell death. In conclusion, it appears that LTX-315 triggers unregulated necrosis, which may contribute to its pro-inflammatory and pro-immune effects.

The oncolytic peptide LTX-315 kills cancer cells through Bax/Bak-regulated mitochondrial membrane permeabilization

Oncotarget 2015 Sep 29;6(29):26599-614.PMID:26378049DOI:10.18632/oncotarget.5613.

LTX-315 has been developed as an amphipathic cationic peptide that kills cancer cells. Here, we investigated the putative involvement of mitochondria in the cytotoxic action of LTX-315. Subcellular fractionation of LTX-315-treated cells, followed by mass spectrometric quantification, revealed that the agent was enriched in mitochondria. LTX-315 caused an immediate arrest of mitochondrial respiration without any major uncoupling effect. Accordingly, LTX-315 disrupted the mitochondrial network, dissipated the mitochondrial inner transmembrane potential, and caused the release of mitochondrial intermembrane proteins into the cytosol. LTX-315 was relatively inefficient in stimulating mitophagy. Cells lacking the two pro-apoptotic multidomain proteins from the BCL-2 family, BAX and BAK, were less susceptible to LTX-315-mediated killing. Moreover, cells engineered to lose their mitochondria (by transfection with Parkin combined with treatment with a protonophore causing mitophagy) were relatively resistant against LTX-315, underscoring the importance of this organelle for LTX-315-mediated cytotoxicity. Altogether, these results support the notion that LTX-315 kills cancer cells by virtue of its capacity to permeabilize mitochondrial membranes.

LTX-315-enabled, radiotherapy-boosted immunotherapeutic control of breast cancer by NK cells

Oncoimmunology 2021 Aug 10;10(1):1962592.PMID:34408925DOI:10.1080/2162402X.2021.1962592.

LTX-315 is a nonameric oncolytic peptide in early clinical development for the treatment of solid malignancies. Preclinical and clinical evidence indicates that the anticancer properties of LTX-315 originate not only from its ability to selectively kill cancer cells, but also from its capacity to promote tumor-targeting immune responses. Here, we investigated the therapeutic activity and immunological correlates of intratumoral LTX-315 administration in three syngeneic mouse models of breast carcinoma, with a focus on the identification of possible combinatorial partners. We found that breast cancer control by LTX-315 is accompanied by a reconfiguration of the immunological tumor microenvironment that supports the activation of anticancer immunity and can be boosted by radiation therapy. Mechanistically, depletion of natural killer (NK) cells compromised the capacity of LTX-315 to limit local and systemic disease progression in a mouse model of triple-negative breast cancer, and to extend the survival of mice bearing hormone-accelerated, carcinogen-driven endogenous mammary carcinomas. Altogether, our data suggest that LTX-315 controls breast cancer progression by engaging NK cell-dependent immunity.