Leelamine hydrochloride
Based on 1 Customer Validation
Leelamine hydrochloride is an orally active weakly basic amine that inhibits NPC1 and the androgen receptor AR-V7, and acts as a cannabinoid receptor agonist. Leelamine hydrochloride also functions as a lysosome affinity agent that blocks endocytosis, disrupts autophagic flux and cholesterol transport, thereby altering the RTK-AKT/STAT/MAPK signaling cascade. Leelamine hydrochloride induces cancer cell death and autophagosome accumulation, and can be used in research related to melanoma, castration-resistant prostate cancer and breast cancer.
For research use only. We do not sell to patients.
- Purity : 98.10%
- CAS No.: 16496-99-4
- Formula: C20H32ClN
- Molecular Weight:321.93
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Storage:
-20°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
Description
IC50 & Target
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CB1 |
In Vitro
Leelamine hydrochloride (6, 10, 100 μM) potently inhibits the proliferation and induces apoptosis of UACC 903 and 1205 Lu metastatic melanoma cells, with IC50 values of 1.35 μM and 1.93 μM for the two cell lines, respectively. Its mechanism of action involves disrupting cholesterol transport and inhibiting oncogenic signaling pathways[1].
Leelamine hydrochloride (1, 2, 3, 4, 5 μM) induces dose-dependent apoptosis in MDA-MB-231, MCF-7 and SUM159 breast cancer cells without affecting normal MCF-10A mammary epithelial cells, and also inhibits the self-renewal of breast cancer stem cells[1].
Leelamine hydrochloride (0.62-100 μmol/L; 72 h) potently kills UACC 903 and 1205 Lu melanoma cells, with IC50 values of 1.35 μmol/L and 1.93 μmol/L, respectively; it shows weak activity against normal FF2441 fibroblasts, with an IC50 of 8.91 μmol/L; its cytotoxic activity can be reversed by bafilomycin A1 or β-cyclodextrin[2].
Leelamine hydrochloride (3, 5, 10 µmol/L; 24 h) induces caspase-independent cell death in UACC 903 and 1205 Lu melanoma cells at concentrations as low as 3 µmol/L, a process that is partially dependent on autophagic flux; BAX-knockout HCT116 cells exhibit increased resistance to it, whereas normal fibroblasts show reduced cell death activity at this concentration; this cell death can be blocked by vacuolar H+-ATPase inhibitors or cholesterol depletion via β-cyclodextrin[3].
Leelamine hydrochloride (3.0-5.0 μmol/L; 24 h) dose-dependently inhibits autophagic flux in UACC 903 melanoma cells, which is confirmed by increased protein levels of p62 and LC3B following treatment with 3.0, 4.0, and 5.0 μmol/L for 24 h[2].
Leelamine hydrochloride (3.0-5.0 μmol/L; 24 h) inhibits the PI3K/AKT, STAT3 and MAPK oncogenic signaling pathways in UACC 903 melanoma cells following 24 h of treatment at concentrations of 3.0, 4.0 and 5.0 μmol/L[2].
Leelamine (3 µmol/L; 30-45 min) acts as a lysosome-targeting compound in UACC 903 melanoma cells, with an uptake rate of 60% within 30 minutes. At a concentration of 3 µmol/L, it reduces the uptake of LysoTracker Red DND-99, and its vacuolating activity is inhibited by vacuolar H+-ATPase inhibitors[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:normal human fibroblast cell line FF2441, human melanoma cell lines UACC 903 and 1205 Lu
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Concentration:0.62-100 μmol/L (72 h viability assay); 10 nmol/L bafilomycin A1, 1 mmol/L β-cyclodextrin (24 h recovery assay)
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Incubation Time:72 h (viability assay); 24 h (recovery assay)
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Result:Potently reduced viability of UACC 903 melanoma cells with an IC50 of 1.35 μmol/L.
Potently reduced viability of 1205 Lu melanoma cells with an IC50 of 1.93 μmol/L.
Reduced viability of normal FF2441 fibroblasts with an IC50 of 8.91 μmol/L.
Reversed leelamine (hydrochloride)-mediated cell death in melanoma cells when co-treated with bafilomycin A1 or β-cyclodextrin.
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Cell Line:human melanoma cell line UACC 903
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Concentration:3.0-5.0 μmol/L
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Incubation Time:24 h
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Result:Dose-dependently induced accumulation of p62 and LC3B proteins in UACC 903 cells.\nInhibited PI3K/AKT signaling, as shown by reduced levels of phosphorylated AKT (Ser473) and phosphorylated PRAS40 (Thr246), along with decreased cyclin D1 and increased cleaved PARP and cleaved caspase-3.
Reduced phosphorylated STAT3 (Tyr705) levels.
Decreased phosphorylated ERK1/2 (Thr202/Tyr204) and phosphorylated CDK2 (Thr160) levels, inhibiting MAPK signaling.
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Cell Line:metastatic melanoma cell lines UACC 903 and 1205 Lu, wild-type and BAX knockout HCT116 human colon cancer cell lines, wild-type and ATG5 knockout mouse embryonic fibroblast (MEF) cell lines, human fibroblast cell line FF2441
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Concentration:3 µmol/L, 5 µmol/L, 10 µmol/L (leelamine); 10 nmol/L Bafilomycin A1 or Concanamycin A (cotreated with leelamine); 20 µmol/L z-VAD-fmk (preincubated before leelamine); 1 mmol/L β-cyclodextrin (pretreated or cotreated with leelamine)
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Incubation Time:24 h (leelamine incubation); 1 h (z-VAD-fmk preincubation); 60 min (β-cyclodextrin pretreatment)
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Result:Induced cell death in melanoma cell lines UACC 903 and 1205 Lu.
Protected these cells from leelamine-mediated death when cotreated with 10 nmol/L Bafilomycin A1 or Concanamycin A.
Failed to rescue UACC 903 cells from leelamine-mediated death when cotreated with the pan-caspase inhibitor z-VAD-fmk, while fully restoring viability of TRAIL-treated control cells.
Rendered BAX knockout HCT116 cells more resistant to leelamine-mediated death than wild-type HCT116 cells.
Caused ATG5 knockout MEFs to show partial resistance to leelamine-mediated death and not undergo vacuolization upon treatment.
Suppressed leelamine-mediated cell death in UACC 903 and 1205 Lu cells when used in pre- or cotreatment with β-cyclodextrin.
Altered cholesterol localization (a marker of leelamine activity) in normal fibroblast cells FF2441 only at 10 µmol/L leelamine, while melanoma cells showed effects at 3 µmol/L.
In Vivo
Leelamine hydrochloride (7.5 mg/kg; intraperitoneal injection; 5 times per week) inhibits the growth of orthotopic SUM159 breast cancer xenografts in female nude mice by 70% without obvious systemic toxicity[1].
Leelamine hydrochloride (80 mg/kg; p.o.; daily; 3-4 weeks) inhibits tumor growth of xenografted melanoma in female athymic nu/nu mice with extremely low systemic toxicity[2].
Leelamine hydrochloride (5-20 mg/kg) increases the activity of hepatic CYP2B enzyme by 4-fold in male mice and upregulates the protein level of CYP2B10[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Nude mice (female)[1]
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Dosage:7.5 mg/kg
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Administration:i.p.; 5 times per week
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Result:Suppressed tumor growth by 70%.
Showed no significant systemic toxicity after treatment.
Caused no changes in body weight, blood parameters, or organ morphology after treatment.
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Animal Model:athymic nu/nu (female, 4-6 weeks old)[2]
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Dosage:80 mg/kg
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Administration:p.o.; daily; 3-4 weeks
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Result:Reduced tumor volume by an amount comparable to the 51% reduction seen with analog compound 4a.
Showed no significant differences in body weights compared to vehicle controls.
Resulted in blood biomarkers of organ toxicity (ALT, AST, ALKP, ALB, GLB, TPR, TBIL, BUN, GLU, CK, CAL) falling within the normal range for this mouse species.
Chemical Information
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CAS No. 16496-99-4
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Appearance Solid
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Molecular Weight 321.93
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Formula C20H32ClN
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Color White to off-white
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SMILES
NC[C@]1(C)CCC[C@]2(C)C3=C(CC[C@@]12[H])C=C(C(C)C)C=C3.Cl
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Structure Classification
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Initial Source
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
-20°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
In Vitro:
DMSO : 25 mg/mL (77.66 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (7.77 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (7.77 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocols
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Mammalian live/dead viability and cytotoxicity staining
Live/dead viability and cytotoxicity staining assays are based on the simultaneous detection of intracellular esterase activity in metabolically active (viable) cells and membrane integrity loss in non-viable cells. In commonly used dual-staining approaches, membrane-permeant fluorogenic substrates are converted by intracellular esterases into fluorescent products in live cells, while impermeant DNA-binding dyes selectively enter cells with compromised plasma membranes and label nucleic acids in dead or dying cells, enabling discrimination between viable and non-viable populations by fluorescence microscopy or flow cytometry.
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Research Protocol for Endocrine Diseases
Endocrine diseases often arise from disrupted hormone production, hormone signaling, or target-tissue responsiveness; for diabetes-focused endocrine disease models, insulin signaling regulates glucose uptake, hepatic glucose output, lipid metabolism, and β-cell compensation. Type 2 diabetes develops through interacting defects in insulin resistance, β-cell dysfunction, adipose inflammation, hepatic glucose overproduction, altered incretin signaling, and ectopic lipid metabolism. A major unresolved question is whether endocrine dysfunction is driven primarily by target-tissue insulin resistance, intrinsic β-cell failure, immune/inflammatory stress, or combined multi-organ failure that differs by disease stage.
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Autophagy
Autophagy is a process in which eukaryotic cells use lysosomes to degrade their own cytoplasmic proteins and damaged organelles under the regulation of autophagy related gene (Atg). Microtubule-associated proteins light chain 3 (LC3) is recognized as autophagy marker, which transfers from cytoplasmic LC3 (LC3-I) to membrane type (LC3-II). LC3-II/I ratio could be detected by Western Blot and fluorescence microscopy.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
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Lysosome and acidic-vesicle live-cell staining
Lysosome and acidic-vesicle live-cell staining detects acidic intracellular compartments by using membrane-permeant acidotropic probes that accumulate in low-pH vesicles, including lysosomes, late endosomes, autolysosomes, and acidic phagosomes. LysoTracker staining is commonly used as an intensity-based readout of acidic lysosomal compartment abundance or enlargement, while acridine orange produces green fluorescence in less concentrated compartments and red fluorescence after concentration-dependent accumulation in acidic vesicular organelles. Loss or reduction of acridine-orange red signal can be used as a readout of lysosomal membrane permeabilization or reduced acidic-vesicle integrity. This protocol is designed for live cultured cells and can be adapted for fluorescence microscopy, high-content imaging, plate-reader readout, or flow cytometry when the selected literature supports the readout. Because these dyes report acidotropic accumulation rather than lysosome identity alone,
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Macroautophagy Solutions
Macroautophagy is a conserved lysosome-dependent degradation pathway in which cytoplasmic material is sequestered into double-membrane autophagosomes and delivered to lysosomes for degradation and recycling. The pathway supports cellular homeostasis during nutrient limitation, organelle stress, protein-aggregate accumulation, infection, differentiation, and tissue remodeling by coupling cargo sequestration, autophagosome maturation, lysosomal fusion, and degradation of cargo-derived macromolecules. The core molecular sequence includes initiation by nutrient- and stress-regulated autophagy machinery, autophagosome nucleation, LC3/ATG8-family conjugation to autophagosomal membranes, cargo selection through receptors such as SQSTM1/p62, autophagosome-lysosome fusion, and lysosomal degradation. LC3 was identified as a mammalian homolog of yeast Atg8 that localizes to autophagosomal membranes after processing, and p62/SQSTM1 was shown to connect ubiquitinated cargo with autophagic degradati
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Breast Cancer Modeling
Breast cancer is a heterogeneous cancer, and it has been distinguished into four subtypes: luminal A, luminal B, HER2-positive and basal-like. Molecular mutations, epigenetic alterations, hormone exposure and immune microenvironment are related to the progression of breast cancer.
Purity & Documentation
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Data Sheet (293 KB)
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SDS (394 KB)
- English - EN (394 KB)
- Français - FR (394 KB)
- Deutsch - DE (394 KB)
- Norwegian - NO (394 KB)
- Español - ES (394 KB)
- Swedish - SV (394 KB)
- Italian - IT (394 KB)
- Korean - KR (394 KB)
- Portuguese - PT (394 KB)
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Handling Instructions (2659 KB)
References
[1]. Merarchi M, et al. A Brief Overview of the Antitumoral Actions of Leelamine. Biomedicines. 2019 Jul 19;7(3):53. [Content Brief]
[2]. Gowda R, et al. Identifying the structure-activity relationship of leelamine necessary for inhibiting intracellular cholesterol transport. Oncotarget. 2017 Apr 25;8(17):28260-28277. [Content Brief]
[3]. Kuzu OF, et al. Leelamine mediates cancer cell death through inhibition of intracellular cholesterol transport. Molecular cancer therapeutics. 2014 Jul;13(7):1690-703. [Content Brief]
[4]. Singh KB, et al. Therapeutic Potential of Leelamine, a Novel Inhibitor of Androgen Receptor and Castration-Resistant Prostate Cancer. Molecular cancer therapeutics. 2018 Oct;17(10):2079-2090. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| DMSO | 1 mM | 3.1063 mL | 15.5313 mL | 31.0627 mL | 77.6566 mL |
| 5 mM | 0.6213 mL | 3.1063 mL | 6.2125 mL | 15.5313 mL | |
| 10 mM | 0.3106 mL | 1.5531 mL | 3.1063 mL | 7.7657 mL | |
| 15 mM | 0.2071 mL | 1.0354 mL | 2.0708 mL | 5.1771 mL | |
| 20 mM | 0.1553 mL | 0.7766 mL | 1.5531 mL | 3.8828 mL | |
| 25 mM | 0.1243 mL | 0.6213 mL | 1.2425 mL | 3.1063 mL | |
| 30 mM | 0.1035 mL | 0.5177 mL | 1.0354 mL | 2.5886 mL | |
| 40 mM | 0.0777 mL | 0.3883 mL | 0.7766 mL | 1.9414 mL | |
| 50 mM | 0.0621 mL | 0.3106 mL | 0.6213 mL | 1.5531 mL | |
| 60 mM | 0.0518 mL | 0.2589 mL | 0.5177 mL | 1.2943 mL |
Leelamine hydrochloride Related Classifications
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