Leelamine
(Synonyms: 脱氢松香胺) 目录号 : GC44048
An inhibitor of pyruvate dehydrogenase kinase
Cas No.:1446-61-3
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
Leelamine is a diterpene molecule whose name derives from the Sanskrit word leela which means "play". It has weak affinity for the human central cannabinoid (CB1) and peripheral cannabinoid (CB2) receptors, exhibiting 20% displacement of [3H]-CP55940 at a concentration of 10 µM. Leelamine inhibits pyruvate dehydrogenase kinase (PDK) with an IC50 value of 9.5 µM. Derivatives of leelamine exhibit anti-inflammatory activity and show moderate inhibition of phospholipase A2 activity from a variety of sources.
| Cas No. | 1446-61-3 | SDF | |
| 别名 | 脱氢松香胺 | ||
| Canonical SMILES | CC(C)C(C=C1)=CC2=C1[C@]3(C)[C@](CC2)([H])[C@@](CN)(C)CCC3 | ||
| 分子式 | C20H31N | 分子量 | 285.5 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,Ethanol: 100 mg/ml,Ethanol:PBS (pH 7.2) (1:3): .25 mg/ml | 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 | 3.5026 mL | 17.5131 mL | 35.0263 mL |
| 5 mM | 0.7005 mL | 3.5026 mL | 7.0053 mL |
| 10 mM | 0.3503 mL | 1.7513 mL | 3.5026 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。
A Brief Overview of the Antitumoral Actions of Leelamine
Biomedicines 2019 Jul 19;7(3):53.PMID:31330969DOI:10.3390/biomedicines7030053.
For the last couple of decades, natural products, either applied singly or in conjunction with other cancer therapies including chemotherapy and radiotherapy, have allowed us to combat different types of human cancers through the inhibition of their initiation and progression. The principal sources of these useful compounds are isolated from plants that were described in traditional medicines for their curative potential. Leelamine, derived from the bark of pine trees, was previously reported as having a weak agonistic effect on cannabinoid receptors and limited inhibitory effects on pyruvate dehydrogenase kinases (PDKs). It has been reported to possess a strong lysosomotropic property; this feature enables its assembly inside the acidic compartments within a cell, such as lysosomes, which may eventually hinder endocytosis. In this review, we briefly highlight the varied antineoplastic actions of Leelamine that have found implications in pharmacological research, and the numerous intracellular targets affected by this agent that can effectively negate the oncogenic process.
Leelamine Exerts Antineoplastic Effects in Association with Modulating Mitogen‑Activated Protein Kinase Signaling Cascade
Nutr Cancer 2022;74(9):3375-3387.PMID:35579498DOI:10.1080/01635581.2022.2059092.
Mitogen‑activated protein kinase (MAPK) pathway is a prominent signaling cascade that modulates cell proliferation, apoptosis, stress response, drug resistance, immune response, and cell motility. Activation of MAPK by various small molecules/natural compounds has been demonstrated to induce apoptosis in cancer cells. Herein, the effect of Leelamine (LEE, a triterpene derived from bark of pine trees) on the activation of MAPK in hepatocellular carcinoma (HCC) and breast cancer (BC) cells was investigated. LEE induced potent cytotoxicity of HCC (HepG2 and HCCLM3) and BC (MDA-MB-231 and MCF7) cells over normal counterparts (MCF10A). LEE significantly enhanced the phosphorylation of p38 and JNK MAPKs in a dose-dependent fashion and it did not affect the phosphorylation of ERK in HCC and BC cells. The apoptosis-driving effect of LEE was further demonstrated by cleavage of procaspase-3/Bid and suppression of prosurvival proteins (Bcl-xL and XIAP). Furthermore, LEE also reduced the SDF1-induced-migration and -invasion of HCC and BC cells. Taken together, the data demonstrated that LEE promotes apoptosis and induces an anti-motility effect by activating p38 and JNK MAPKs in HCC and BC cells.
Leelamine Modulates STAT5 Pathway Causing Both Autophagy and Apoptosis in Chronic Myelogenous Leukemia Cells
Biology (Basel) 2022 Feb 25;11(3):366.PMID:35336740DOI:10.3390/biology11030366.
Leelamine (LEE) has recently attracted significant attention for its growth inhibitory effects against melanoma, breast cancer, and prostate cancer cells; however, its impact on hematological malignancies remains unclear. Here, we first investigate the cytotoxic effects of LEE on several human chronic myeloid leukemia (CML) cells. We noted that LEE stimulated both apoptosis and autophagy in CML cells. In addition, the constitutive activation of signal transducer and activator of transcription 5 (STAT5) was suppressed substantially upon LEE treatment. Moreover, STAT5 knockdown with small interfering RNA (siRNA) increased LEE-induced apoptosis as well as autophagy and affected the levels of various oncogenic proteins. Thus, the targeted mitigation of STAT5 activation by LEE can contribute to its diverse anticancer effects by enhancing two distinct cell death pathways.
Leelamine suppresses cMyc expression in prostate cancer cells in vitro and inhibits prostate carcinogenesis in vivo
J Cancer Metastasis Treat 2021;7:16.PMID:34660908DOI:10.20517/2394-4722.2021.08.
Aim: Leelamine (LLM) inhibits growth of human prostate cancer cells but the underlying mechanism is not fully understood. The present study was undertaken to determine the effect of LLM on cMyc, which is overexpressed in a subset of human prostate cancers. Methods: The effect of LLM on cMyc expression and activity was determined by western blotting/confocal microscopy and luciferase reporter assay, respectively. A transgenic mouse model of prostate cancer (Hi-Myc) was used to determine chemopreventive efficacy of LLM. Results: Exposure of androgen sensitive (LNCaP) and castration-resistant (22Rv1) human prostate cancer cells to LLM resulted in downregulation of protein and mRNA levels of cMyc. Overexpression of cMyc partially attenuated LLM-mediated inhibition of colony formation, cell viability, and cell migration in 22Rv1 and/or PC-3 cells. LLM treatment decreased protein levels of cMyc targets (e.g., lactate dehydrogenase), however, overexpression of cMyc did not attenuate these effects. A trend for a decrease in expression level of cMyc protein was discernible in 22Rv1 xenografts from LLM-treated mice compared with control mice. The LLM treatment (10 mg/kg body weight, 5 times/week) was well-tolerated by Hi-Myc transgenic mice. The incidence of high-grade prostatic intraepithelial neoplasia, adenocarcinoma in situ, and microinvasion was lower in LLM-treated Hi-Myc mice but the difference was not statistically significant. Conclusion: The present study reveals that LLM inhibits cMyc expression in human prostate cancer cells in vitro but concentrations higher than 10 mg/kg may be required to achieve chemoprevention of prostate cancer.
Leelamine mediates cancer cell death through inhibition of intracellular cholesterol transport
Mol Cancer Ther 2014 Jul;13(7):1690-703.PMID:24688051DOI:10.1158/1535-7163.MCT-13-0868.
Leelamine is a promising compound for the treatment of cancer; however, the molecular mechanisms leading to leelamine-mediated cell death have not been identified. This report shows that Leelamine is a weakly basic amine with lysosomotropic properties, leading to its accumulation inside acidic organelles such as lysosomes. This accumulation leads to homeostatic imbalance in the lysosomal endosomal cell compartments that disrupts autophagic flux and intracellular cholesterol trafficking as well as receptor-mediated endocytosis. Electron micrographs of leelamine-treated cancer cells displayed accumulation of autophagosomes, membrane whorls, and lipofuscin-like structures, indicating disruption of lysosomal cell compartments. Early in the process, leelamine-mediated killing was a caspase-independent event triggered by cholesterol accumulation, as depletion of cholesterol using β-cyclodextrin treatment attenuated the cell death and restored the subcellular structures identified by electron microscopy. Protein microarray-based analyses of the intracellular signaling cascades showed alterations in RTK-AKT/STAT/MAPK signaling cascades, which was subsequently confirmed by Western blotting. Inhibition of Akt, Erk, and Stat signaling, together with abnormal deregulation of receptor tyrosine kinases, was caused by the inhibition of receptor-mediated endocytosis. This study is the first report demonstrating that Leelamine is a lysosomotropic, intracellular cholesterol transport inhibitor with potential chemotherapeutic properties leading to inhibition of autophagic flux and induction of cholesterol accumulation in lysosomal/endosomal cell compartments. Importantly, the findings of this study show the potential of Leelamine to disrupt cholesterol homeostasis for treatment of advanced-stage cancers.