| Size | Price | |
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| Other Sizes |
| Targets |
The study does not identify a direct molecular target. Leelamine is a lysosomotropic agent that accumulates in lysosomes, blocking cholesterol translocation. This indirectly inhibits multiple oncogenic signaling pathways, including RTK-AKT/STAT3/MAPK and AKT/mTOR. It also has weak agonistic effects on cannabinoid receptors and limited inhibitory effects on pyruvate dehydrogenase kinases. [1]
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| ln Vitro |
Leelamine exhibits antiproliferative effects in various cancer cell lines. In melanoma UACC 903 and 1205 Lu cells, IC50 values were 1.35 ± 0.1 μM and 1.93 ± 0.2 μM, respectively. [1]
In melanoma cells, leelamine inhibits PI3K/Akt, MAPK, and STAT3 pathways through suppression of intracellular cholesterol transport. It attenuates phosphorylation of Erk, CREB, RPS6KB1 (p70S6K), EIF4EBP1 (4E-BP1), and STATs, and inhibits mTOR signaling. It also induces G0-G1 phase cell cycle arrest. [1] In breast cancer cells (MDA-MB-231, MCF-7, SUM159), leelamine induces apoptosis in a dose-dependent manner (0-5 μM), with induction of proapoptotic proteins Bax and Bak, activation of caspase-9, and cytosolic release of cytochrome c. Normal mammary epithelial cells (MCF-10A) were resistant to these effects. Leelamine also suppresses breast cancer stem cell self-renewal ability. [1] In prostate cancer cell lines (LNCaP, C4-2B, 22Rv1, Myc-CaP), leelamine decreases mitotic activity and prostate-specific antigen expression, and induces apoptosis. It inhibits mRNA and protein expression of androgen receptor and its splice variants, including AR-V7. In silico studies suggest interaction with Y739 in AR. [1] Leelamine causes cholesterol accumulation in lysosomes, which abrogates receptor-mediated endocytosis and endosome trafficking. [1] |
| ln Vivo |
In nude mice bearing UACC 903 or 1205 Lu melanoma xenografts, leelamine treatment (80 mg/kg body weight) reduced tumor size by approximately 50% and decreased proliferation. [1]
In female nude mice with SUM159 breast cancer xenografts, leelamine treatment (7.5 mg/kg body weight, 5 times/week) suppressed tumor growth by approximately 70% without any systemic toxicity. [1] In a 22Rv1 prostate cancer xenograft model, leelamine inhibited tumor growth and decreased PSA secretion. It also decreased Ki-67 expression, mitotic activity, and AR variant expression in tumor tissues. [1] In male mice liver, leelamine treatment (5, 10, or 20 mg/kg) increased CYP2B activity by almost 4-fold compared to controls and significantly increased CYP2B10 protein levels without major changes in mRNA levels. [1] |
| Enzyme Assay |
It summarizes findings from previous studies, including the identification of CYP2D6 as the dominant CYP enzyme responsible for the biotransformation of leelamine to its mono-hydroxylated metabolite. [1]
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| Cell Assay |
The review summarizes cell-based assays from previous studies, including MTS assays for cell viability, flow cytometry for cell cycle analysis, Western blotting for protein expression analysis, and apoptosis assays. Specific protocols are not detailed in this review. [1]
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| Animal Protocol |
The review summarizes in vivo studies from previous publications. In melanoma xenograft models, nude mice bearing UACC 903 or 1205 Lu tumors were treated with leelamine at 80 mg/kg body weight. [1]
* In breast cancer xenograft models, female nude mice with orthotopic SUM159 tumors were treated with leelamine at 7.5 mg/kg body weight, administered 5 times per week via intraperitoneal injection. [1] * In prostate cancer xenograft models, mice bearing 22Rv1 tumors were treated with leelamine, resulting in tumor growth inhibition. [1] * For CYP2B induction studies, male mice were treated with leelamine at 5, 10, or 20 mg/kg, and liver tissue was analyzed for CYP2B activity and protein expression. [1] The review summarizes in vivo studies from previous publications. In melanoma xenograft models, nude mice bearing UACC 903 or 1205 Lu tumors were treated with leelamine at 80 mg/kg body weight. [1] In breast cancer xenograft models, female nude mice with orthotopic SUM159 tumors were treated with leelamine at 7.5 mg/kg body weight, administered 5 times per week via intraperitoneal injection. [1] In prostate cancer xenograft models, mice bearing 22Rv1 tumors were treated with leelamine, resulting in tumor growth inhibition. [1] For CYP2B induction studies, male mice were treated with leelamine at 5, 10, or 20 mg/kg, and liver tissue was analyzed for CYP2B activity and protein expression. [1] |
| ADME/Pharmacokinetics |
Leelamine undergoes phase 1 metabolism, producing a mono-hydroxylated metabolite at the C9 carbon of the octahydrophenanthrene ring (M1). [1]
CYP2D6 was identified as the dominant CYP enzyme responsible for the biotransformation of leelamine to its hydroxylated metabolite. [1] Only one metabolite has been identified in urine, and none in feces, suggesting that leelamine is metabolized to a mono-hydroxyl metabolite by CYP2D6 and principally excreted in the urine. [1] |
| Toxicity/Toxicokinetics |
In melanoma xenograft studies, body weights of mice treated with leelamine (80 mg/kg daily for 22 days) showed no significant differences compared to control groups. Blood parameters measured after this period showed no organ-related toxicity. [1]
Histological analysis of liver, spleen, kidney, intestine, lung, and heart from leelamine-treated mice showed no modifications in morphology or overall structure. [1] In breast cancer xenograft studies, intraperitoneal administration of leelamine (7.5 mg/kg, 5 times/week) suppressed tumor growth without any significant toxicity. [1] Both in vitro and in vivo studies have shown negligible toxicity with leelamine treatment. [1] |
| References | |
| Additional Infomation |
[(1R,4aS,10aR)-1,4a-dimethyl-7-propyl-2-yl-2,3,4,9,10,10a-hexahydrophenanthrene-1-yl]methylamine is a diterpenoid compound. See also: liramin (note moved to).
Leelamine is a lipophilic diterpene amine phytochemical (pKa of 9.9) extracted from the bark of pine trees. [1] It possesses strong lysosomotropic properties due to its basic and lipophilic characteristics, enabling its accumulation inside acidic cellular compartments such as lysosomes. [1] The amino group of leelamine is responsible for its lysosomotropic and antitumorigenic effects; suppression of the amino group or its charge leads to loss of antineoplastic actions. [1] Leelamine indirectly targets various oncogenic signaling pathways by blocking cholesterol translocation from lysosomes to cytoplasm, making cholesterol unavailable for cancer cell activities. [1] A liposomal formulation of leelamine, called Nanolipolee-007, has been shown to reduce melanoma metastasis and induce apoptosis independently of BRAF mutational status. [1] Recent studies suggest a potential application of leelamine as an antidiabetic agent through induction of cytochrome P450 2B6 activity. [1] |
| Molecular Formula |
C20H31N
|
|---|---|
| Molecular Weight |
285.47
|
| Exact Mass |
285.245
|
| CAS # |
1446-61-3
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| Related CAS # |
Leelamine hydrochloride;16496-99-4
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| PubChem CID |
62034
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| Appearance |
Colorless to light yellow <44.5°C powder,>44.5°C liquid
|
| Density |
1.0±0.1 g/cm3
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| Boiling Point |
382.9±11.0 °C at 760 mmHg
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| Melting Point |
44.50℃
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| Flash Point |
156.7±9.1 °C
|
| Vapour Pressure |
0.0±0.9 mmHg at 25°C
|
| Index of Refraction |
1.528
|
| LogP |
6.4
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| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
1
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
21
|
| Complexity |
376
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
N([H])([H])C([H])([H])[C@]1(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])[C@]2(C([H])([H])[H])C3C([H])=C([H])C(C([H])(C([H])([H])[H])C([H])([H])[H])=C([H])C=3C([H])([H])C([H])([H])[C@]21[H]
|
| InChi Key |
JVVXZOOGOGPDRZ-SLFFLAALSA-N
|
| InChi Code |
InChI=1S/C20H31N/c1-14(2)15-6-8-17-16(12-15)7-9-18-19(3,13-21)10-5-11-20(17,18)4/h6,8,12,14,18H,5,7,9-11,13,21H2,1-4H3/t18-,19-,20+/m0/s1
|
| Chemical Name |
[(1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthren-1-yl]methanamine
|
| Synonyms |
NSC 2955 NSC2955 Dehydroabietylamine Leelamine NSC-2955Leelamine free base
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~350.30 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.76 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (8.76 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (8.76 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5030 mL | 17.5150 mL | 35.0300 mL | |
| 5 mM | 0.7006 mL | 3.5030 mL | 7.0060 mL | |
| 10 mM | 0.3503 mL | 1.7515 mL | 3.5030 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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