Lys05, or Lys01 trihydrochloride, is a potent, water soluble lysosomal autophagy inhibitor. Lys05 is a previously undescribed dimeric chloroquine which more potently accumulates in the lysosome and blocks autophagy compared with HCQ. Lys05 produced more potent antitumor activity as a single agent both in vitro and in vivo in multiple human cancer cell lines and xenograft models compared with HCQ. Lys05 is therefore a new lysosomal autophagy inhibitor that has potential to be developed further into a drug for cancer and other medical applications.
Physicochemical Properties
| Molecular Formula | C23H26CL5N5 |
| Molecular Weight | 549.75 |
| Exact Mass | 547.063 |
| CAS # | 1391426-24-6 |
| Related CAS # | Lys01;1391426-22-4 |
| PubChem CID | 70673566 |
| Appearance | Light brown to gray solid powder |
| Hydrogen Bond Donor Count | 5 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 33 |
| Complexity | 480 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | N1=CC=C(NCCN(CCNC2C3C=CC(=CC=3N=CC=2)Cl)C)C2C=CC(=CC1=2)Cl.Cl.Cl.Cl |
| InChi Key | N2-(7-Chloro-4-quinolinyl)-N1-[2-[(7-chloro-4-quinolinyl)amino]ethyl]-N1-methyl-1,2-ethanediamine trihydrochloride |
| InChi Code | JTUYDBHQGOZPQQ-UHFFFAOYSA-N |
| Chemical Name | LYS-05 HCl LYS05 LYS-05 Lys01 (trihydrochloride) Lys01 HCl salt. |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| 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]. |
| 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]. |
| 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 |
Solubility Data
| Solubility (In Vitro) |
DMSO : ~25 mg/mL (~45.48 mM) H2O : ~6.4 mg/mL (~11.64 mM) |
| 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. 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. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| 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 |