LYN-1604

SKU: orb1225706

Description

LYN-1604 is a potential ULK1 agonist (enzymatic activity=195.7% at 100 nM and IC50=1.66 uM against MDA-MB-231 cells), displays a good effect on ULK1 activation with an EC50 of 18.94 nM; induces cell death, associated with autophagy by the ULK complex (ULK1-mATG13-FIP200-ATG101) in MDA-MB-231 cells; induces cell death involved in ATF3, RAD21, and caspase3, accompanied by autophagy and apoptosis; inhibits the growth of xenograft TNBC.

Research Area

Signal Transduction

Key Properties

• CAS Number: 2088939-99-3
• MW: 584.626
• Purity: >98% (HPLC)
• Formula: C₃₃H₄₃Cl₂N₃O₂
• SMILES: CC(C)CN(CC(C)C)CC(=O)N1CCN(CC1)CC(C2=C(C=C(C=C2)Cl)Cl)OCC3=CC4=CC=CC=C4C=C3
• Target: ULK
• Solubility: DMSO: 46 mg/mL (78.7 mM); Water: 90 mg/mL (153.9 mM) （ < 1 mg/ml refers to the product slightly soluble or insoluble )

Bioactivity

• In Vivo:
  LYN-1604 (low dose, 25 mg/kg; median dose, 50 mg/kg; high dose, 100 mg/kg; intragastric administration once a day for 14 days) inhibits the growth of xenograft TNBC by targeting ULK1-modulated cell death. Animal model: 24 female nude mice (BALB/c, 6-8 weeks, 20-22 g). Dosage: Low dose, 25 mg/kg; median dose, 50 mg/kg; high dose, 100 mg/kg. Administration: Intragastric administration; once a day for 14 days. Result: Significantly 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 Vitro:
  LYN-1604 is a potential ULK1 agonist (enzymatic activity=195.7% at 100 nM and IC50 = 1.66 μM against MDA-MB-231 cells). LYN-1604 binds to wild-type ULK1 with a binding affinity in the nanomole range (KD=291.4 nM). LYN-1604 (0.5, 1.0 and 2.0 μM) induces cell death via the ULK complex in MDA-MB-231 cells. LYN-1604 (0.5-2 μM, 24 hours) induces remarkable up-regulation of Beclin-1 and degradation of p62, as well as transformation of LC3-I to LC3-II in MDA-MB-231 cells. LYN-1604 induces ATG5-dependent autophagy via the ULK complex. LYN-1604 can also increase cleavage of caspase3 and induce apoptosis. Cell Viability Assay Cell line: MDA-MB-231 cells. Concentration: 0.5, 1.0 and 2.0 μM Incubation time: Result: Induced cell death. Autophagy ratio was increased in a dose-dependent manner. Western blot analysis. Cell line: MDA-MB-231 cells. Concentration: 0, 0.5, 1, and 2 μM Incubation time: 24 hours. Result: Induced remarkable up-regulation of Beclin-1 and degradation of p62, as well as transformation of LC3-I to LC3-II.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

LYN1604

Quick Database Links

Gene Symbol

ULK