| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
| Targets |
Lys05 targets the lysosomal compartment. It accumulates in lysosomes due to its basic, lysosomotropic properties, leading to lysosomal deacidification and inhibition of autophagosome-lysosome fusion. This results in blockade of autophagic flux. The compound is considered a more potent autophagy inhibitor than chloroquine or hydroxychloroquine.
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| ln Vitro |
The autophagy inhibitor Lys01 is ten times more effective than HCQ. Compared to HCQ, Lys01's water-soluble salt, Lys05, accumulates and deacidifies lysosomes more effectively. In MTT experiments, Lys01 and Lys05 result in the same IC50 values, accumulation of the autophagy cargo protein p62, and dose-dependent increases in the LC3II/LC3I ratio [1].
In vitro, Lys05 is a potent autophagy inhibitor that accumulates in lysosomes. It induces lysosomal membrane permeabilization and cell death in cancer cells, particularly those that are dependent on autophagy for survival. The compound shows anti-proliferative activity against various cancer cell lines with greater potency than hydroxychloroquine. |
| ln Vivo |
No mice died from this high-dose, short-term treatment; nevertheless, mice treated with Lys05 76 mg/kg ip showed signs of lethargy and bent backs two days after dosing. Large AVs were found morphologically in cells with intact nuclear and cytoplasmic membranes in Lys05-treated tumors, as demonstrated by electron microscopy. When compared to controls, Lys05-treated tumors showed a substantial reduction in tumor growth. When compared to vehicle-treated controls, the mean daily tumor growth rate decreased by 53% after receiving Lys05 therapy. When HCQ- and Lys05-treated tumors were compared to control-treated tumors at the end of their 14-day therapy, there was a noticeable three-fold and six-fold increase in AV accumulation [1].
In vivo, Lys05 has shown antitumor activity in mouse xenograft models. It inhibits autophagy in tumors and enhances the efficacy of chemotherapy. The compound is more potent than hydroxychloroquine in vivo and achieves higher lysosomal concentrations. Detailed dosing and efficacy data is available in the primary literature. |
| Enzyme Assay |
Non-cellular assays for Lys05 are not typically performed as it is not an enzyme inhibitor. Lysosomal accumulation can be assessed using fluorescent probes. The compound's lysosomotropic properties can be characterized by measuring its basicity and membrane permeability.
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| Cell Assay |
In vitro cellular experiments involve treating cancer cell lines with Lys05 trihydrochloride. Autophagy inhibition is assessed by measuring LC3-II accumulation and p62/SQSTM1 levels by Western blot. Lysosomal function is evaluated using Lysotracker Red or acridine orange staining. Cell viability and apoptosis are measured by standard assays.
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| Animal Protocol |
In vivo animal studies involve tumor xenograft models in mice. Lys05 is administered via intraperitoneal or oral routes. Tumor volume is measured over time to assess antitumor efficacy. Autophagy inhibition in tumors is confirmed by immunohistochemical analysis of LC3 and p62. Combination studies with chemotherapy are also performed.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for Lys05 is limited. The compound accumulates in lysosomes, resulting in high intracellular concentrations. The trihydrochloride salt form improves aqueous solubility. Detailed PK parameters have been reported in the primary literature.
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| Toxicity/Toxicokinetics |
Lys05 trihydrochloride is a research chemical with moderate toxicity. As a lysosomotropic agent, it may cause lysosomal-related toxicity at higher doses. Appropriate safety precautions should be taken during handling. Detailed toxicity data is available in the primary literature.
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| References |
[1]. McAfee Q, et al. Autophagy inhibitor Lys05 has single-agent antitumor activity and reproduces the phenotype of a genetic autophagy deficiency. Proc Natl Acad Sci U S A. 2012 May 22;109(21):8253-8
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| Additional Infomation |
Lys05 trihydrochloride is a potent lysosomotropic autophagy inhibitor structurally related to hydroxychloroquine. It is more potent than chloroquine and hydroxychloroquine in inhibiting autophagy and has shown antitumor activity. This product is for research purposes only and is not for human therapeutic use.
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| Molecular Formula |
C23H26CL5N5
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|---|---|
| Molecular Weight |
549.75
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| Exact Mass |
547.063
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| CAS # |
1391426-24-6
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| Related CAS # |
Lys01;1391426-22-4
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| PubChem CID |
70673566
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| Appearance |
Light brown to gray solid powder
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
33
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| Complexity |
480
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1=CC=C(NCCN(CCNC2C3C=CC(=CC=3N=CC=2)Cl)C)C2C=CC(=CC1=2)Cl.Cl.Cl.Cl
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| InChi Key |
N2-(7-Chloro-4-quinolinyl)-N1-[2-[(7-chloro-4-quinolinyl)amino]ethyl]-N1-methyl-1,2-ethanediamine trihydrochloride
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| InChi Code |
JTUYDBHQGOZPQQ-UHFFFAOYSA-N
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| Chemical Name |
LYS-05 HCl LYS05 LYS-05 Lys01 (trihydrochloride) Lys01 HCl salt.
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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: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 : ~25 mg/mL (~45.48 mM)
H2O : ~6.4 mg/mL (~11.64 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 7.5 mg/mL (13.64 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 75.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: ≥ 4.17 mg/mL (7.59 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 41.7 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.55 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 | 1.8190 mL | 9.0950 mL | 18.1901 mL | |
| 5 mM | 0.3638 mL | 1.8190 mL | 3.6380 mL | |
| 10 mM | 0.1819 mL | 0.9095 mL | 1.8190 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.
Products are for research use only; We do not sell to patients
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