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Purity: ≥98%
LYN-1604 (LYN1604) is a potent agonist or activator of the UNC-51-like kinase 1 (ULK1) with potential antitumor activity. It activates ULK1 with an EC50 of 18.94 nM. ULK1 is well-known to initiate autophagy, and the downregulation of ULK1 has been found in most breast cancer tissues. LYN-1604 interacts with three amino acid residues (LYS50, LEU53, and TYR89) in the activation site of ULK1 as monitored by site-directed mutagenesis and biochemical assays. LYN-1604 could induce cell death, associated with autophagy by the ULK complex (ULK1-mATG13-FIP200-ATG101) in MDA-MB-231 cells. LYN-1604 induced cell death involved in ATF3, RAD21, and caspase3, accompanied by autophagy and apoptosis. LYN-1604 has potential for good therapeutic effects on TNBC by targeting ULK1-modulated cell death in vivo; thus making this ULK1 agonist a novel potential small-molecule drug candidate for future TNBC therapy.
| ln Vitro |
LYN-1604 has the potential to be an agonist for ULK1 (enzymatic activity = 195.7% at 100 nM and IC50 = 1.66 μM against MDA-MB-231 cells) [1]. With an affinity for binding in the nanomole range (KD=291.4 nM), LYN-1604 binds to wild-type ULK1 [1]. On MDA-MB-231 cells, LYN-1604 (0.5, 1.0, and 2.0 μM) causes cell death through the ULK complex[1].. hours) dramatically increases Beclin-1 expression, degrades p62, and causes LC3-I to become LC3-II in MDA-MB-231 cells[1]. Via the ULK complex, LYN-1604 triggers autophagy that is ATG5-dependent[1]. Additionally, LYN-1604 has the ability to trigger apoptosis and boost caspase3 cleavage[1].
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| ln Vivo |
Targeting ULK1-modulated cell death, LYN-1604 (low dose: 25 mg/kg; medium dose: 50 mg/kg; high dose: 100 mg/kg) is an intragastric drug administered once daily for 14 days that reduces the growth of xenograft TNBC [1].
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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. |
| 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. |
| References |
[1]. Zhang L, et al. Discovery of a small molecule targeting ULK1-modulated cell death of triple negative breast cancer in vitro and in vivo. Chem Sci. 2017 Apr 1;8(4):2687-2701.
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| Molecular Formula |
C33H43CL2N3O2
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| Molecular Weight |
584.63
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| CAS # |
2088939-99-3
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| Related CAS # |
LYN-1604 dihydrochloride;2310109-38-5;LYN-1604 hydrochloride;2216753-86-3
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| SMILES |
ClC1=CC=C(C(CN2CCN(C(CN(CC(C)C)CC(C)C)=O)CC2)OCC3=CC=C(C=CC=C4)C4=C3)C(Cl)=C1
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7105 mL | 8.5524 mL | 17.1048 mL | |
| 5 mM | 0.3421 mL | 1.7105 mL | 3.4210 mL | |
| 10 mM | 0.1710 mL | 0.8552 mL | 1.7105 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.
dentification of LYN-1604 as a potent ULK1 agonist, and its binding mode.Chem Sci.2017 Apr 1;8(4):2687-2701. |
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LYN-1604 induces cell death in MDA-MB-231 cells.Chem Sci.2017 Apr 1;8(4):2687-2701. |
 LYN-1604 induces ATG5-dependent autophagyviathe ULK complex.Chem Sci.2017 Apr 1;8(4):2687-2701. |
 LYN-1604 induces autophagy involved in ATF3, RAD21, and caspase3.Chem Sci.2017 Apr 1;8(4):2687-2701. |
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 LYN-1604 has therapeutic potential, targeting ULK-modulated cell deathin vivo.Chem Sci.2017 Apr 1;8(4):2687-2701. |
 Biological evaluation of candidate ULK1 agonists toward human breast cancer cells.Chem Sci.2017 Apr 1;8(4):2687-2701. |
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