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| Targets |
LYN-1604 diHCl targets UNC-51-like kinase 1 (ULK1), a key initiator of autophagy. ULK1 is a serine/threonine kinase that plays a critical role in the induction of autophagy in response to cellular stress. By activating ULK1, LYN-1604 induces autophagy and apoptosis, leading to cell death. ULK1 is downregulated in most breast cancer tissues, making it a promising target for cancer therapy. The compound’s mechanism involves activation of ATF3, RAD21, and caspase3.
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| ln Vitro |
LYN-1604 exhibits potential as an agonist of ULK1 (enzyme activity at 100 nM = 195.7%, IC50 against MDA-MB-231 cells = 1.66 μM) [1]. With an affinity for binding in the nanomolar range (KD=291.4 nM), LYN-1604 binds to wild-type ULK1 [1]. Via the ULK complex, LYN-1604 (0.5, 1.0, and 2.0 μM) causes cell death in MDA-MB-231 cells [1]. In MDA-MB-231 cells, LYN-1604 (0.5-2 μM, 24 hours) leads to a notable increase of Beclin-1, p62 degradation, and the conversion of LC3-I to LC3-II [1]. Via the ULK complex, LYN-1604 triggers autophagy that is ATG5-dependent [1]. Additionally, LYN-1604 has the ability to trigger apoptosis and promote caspase3 cleavage [1].
LYN-1604 diHCl exhibits potent in vitro activity as a ULK1 activator. It has an EC50 of 18.94 nM for ULK1 activation. The compound induces cell death through activation of ATF3, RAD21, and caspase3, accompanied by autophagy and apoptosis. In MDA-MB-231 cells, LYN-1604 demonstrates potent activity. These in vitro activities confirm its potential as an anticancer agent, particularly for triple-negative breast cancer. |
| ln Vivo |
LYN-1604 dihydrochloride, administered intragastrically once daily for 14 days at low, middle, and high doses of 25 mg/kg, 50 mg/kg, and 100 mg/kg, inhibited the growth of xenografted TNBC by targeting ULK1 and modulating cell death [1].
LYN-1604 diHCl has demonstrated in vivo activity in animal models of triple-negative breast cancer (TNBC). The compound targets ULK1-regulated cell death pathways and shows potential therapeutic effects against TNBC. In vivo studies have confirmed that LYN-1604 exhibits good antitumor activity. The compound’s ability to induce autophagy and apoptosis through ULK1 activation contributes to its anticancer efficacy. |
| Enzyme Assay |
In vitro enzyme assays for LYN-1604 diHCl involve measuring its activation of ULK1 kinase activity. These assays typically use recombinant ULK1 and a peptide substrate. The kinase is incubated with ATP and the substrate in the presence of varying concentrations of LYN-1604. The phosphorylation of the substrate is measured to determine the EC50 (18.94 nM). These assays confirm the compound’s mechanism as a ULK1 activator.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: MDA-MB-231 cells Tested Concentrations: 0.5, 1.0 and 2.0 μM Incubation Duration: Experimental Results: Induced cell death. Autophagy ratio was increased in a dose-dependent manner. Western Blot Analysis[1] Cell Types: MDA-MB-231 cells Tested Concentrations: 0, 0.5, 1, and 2 μM Incubation Duration: 24 hrs (hours) Experimental Results: Induced remarkable up-regulation of Beclin-1 and degradation of p62, as well as transformation of LC3-I to LC3 -II. In vitro cellular assays for LYN-1604 diHCl are conducted in cancer cell lines, particularly MDA-MB-231 triple-negative breast cancer cells. Cells are treated with the compound at various concentrations, and ULK1 activation is measured by assessing autophagy markers (LC3-II, p62) and apoptosis markers (caspase3, PARP). Cell viability is measured using MTT or CellTiter-Glo assays. These assays characterize the compound’s anticancer activity. |
| Animal Protocol |
Animal/Disease Models: 24 female nude mice (BALB/c, 6-8 weeks, 20-22 g)[1]
Doses: Low dose, 25 mg/kg; median dose, 50 mg/kg; high dose, 100 mg/kg Route of Administration: intragastric (po) administration; one time/day for 14 days Experimental Results: Dramatically inhibited the growth of xenograft MDA-MB-231 cells. The body weights of mice were stable. By the end of the experiment, the liver and spleen weight indexes of mice were slightly increased in parts of the groups, while the kidney weight index was not affected in all dose groups. In vivo animal experiments with LYN-1604 diHCl are conducted in mouse xenograft models of triple-negative breast cancer. Immunodeficient mice are engrafted with TNBC cells (e.g., MDA-MB-231). LYN-1604 is administered via injection at varying doses. Tumor growth is measured over time, and tumor tissues are harvested for analysis of autophagy and apoptosis markers. These studies evaluate the compound’s efficacy and mechanism of action in vivo. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for LYN-1604 diHCl are limited. The compound has a molecular weight of 657.54 and is soluble in DMSO. Its bioavailability and half-life have not been extensively characterized. The compound is typically stored at -20°C. Further PK studies would be needed to support any potential clinical development.
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| Toxicity/Toxicokinetics |
LYN-1604 diHCl is considered to have low toxicity based on its use as a research compound. However, comprehensive toxicological evaluations have not been extensively published. The compound is intended for research use only and is not approved for human therapeutic use. Standard laboratory safety precautions should be followed when handling this compound. Further toxicity studies would be required to support any potential clinical development.
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| References | |
| Additional Infomation |
LYN-1604 diHCl is a potent activator of UNC-51-like kinase 1 (ULK1) with an EC50 of 18.94 nM. It induces cell death through autophagy and apoptosis and has potential therapeutic applications in triple-negative breast cancer. The compound is also known as LYN-1604 dihydrochloride. It is available in high purity (≥98%) for research applications. Its potent ULK1 activation makes it a valuable tool for studying autophagy and cancer biology.
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| Molecular Formula |
C33H45CL4N3O2
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| Molecular Weight |
657.541305303574
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| Exact Mass |
657.223
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| CAS # |
2310109-38-5
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| Related CAS # |
LYN-1604;2088939-99-3;LYN-1604 hydrochloride;2216753-86-3
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| PubChem CID |
131954512
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
42
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| Complexity |
750
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=C(C=CC=1C(CN1CCN(C(CN(CC(C)C)CC(C)C)=O)CC1)OCC1C=CC2C=CC=CC=2C=1)Cl.Cl.Cl
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| InChi Key |
GZCBLOPFZPJUOQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C33H43Cl2N3O2.2ClH/c1-24(2)19-37(20-25(3)4)22-33(39)38-15-13-36(14-16-38)21-32(30-12-11-29(34)18-31(30)35)40-23-26-9-10-27-7-5-6-8-28(27)17-26;;/h5-12,17-18,24-25,32H,13-16,19-23H2,1-4H3;2*1H
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| Chemical Name |
2-[bis(2-methylpropyl)amino]-1-[4-[2-(2,4-dichlorophenyl)-2-(naphthalen-2-ylmethoxy)ethyl]piperazin-1-yl]ethanone;dihydrochloride
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| Synonyms |
LYN1604 diHCl LYN 1604 diHCl
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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) |
H2O : ~50 mg/mL (~76.04 mM)
DMSO : ~50 mg/mL (~76.04 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.80 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 (3.80 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5208 mL | 7.6041 mL | 15.2082 mL | |
| 5 mM | 0.3042 mL | 1.5208 mL | 3.0416 mL | |
| 10 mM | 0.1521 mL | 0.7604 mL | 1.5208 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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