BL-918
Names
[ CAS No. ]:
2101517-69-3
[ Name ]:
BL-918
[Synonym ]:
(2R)-2-({[3,5-Bis(trifluoromethyl)phenyl]carbamothioyl}amino)-N-(2,4-difluorophenyl)-2-phenylacetamide
Benzeneacetamide, α-[[[[3,5-bis(trifluoromethyl)phenyl]amino]thioxomethyl]amino]-N-(2,4-difluorophenyl)-, (αR)-
Biological Activity
[Description]:
BL-918 is a small molecule activator of ULK1 with EC50 of 24 nM (243% kinase activity at 100 nM), induces autophagy via the ULK complex in SH-SY5Y cells; displays a cytoprotective effect on MPP+-treated SH-SY5Y cells, as well as protected against MPTP-induced motor dysfunction and loss of dopaminergic neurons by targeting ULK1-modulated autophagy in mouse models of PD.
[Related Catalog]:
[Target]
ULK1:24.14 nM (EC50)
[In Vitro]
BL-918 (5 μM; for 24 hours) induces autophagy in Neuron-Like cells[1]. BL-918 (0.5-50 μM; for 24 hours) can partially reverse MPP+-induced cell death, which is determined by enhancing cell viability[1]. BL-918 (5 μM; for 6-36 hours) time-dependently elevates the expression levels of LC3-II, Beclin-1, and its phosphorylation status, whereas reduces the level of the selective autophagy substrate SQSTM1/p62. BL-918 elevates Ser317 and Ser555 phosphorylation of ULK1, as well as decreases Ser757 phosphorylation of ULK1[1]. BL-918 binds to ULK1 with a high binding affinity (KD=0.719 μM)[1]. Cell Autophagy Assay[1] Cell Line: SH-SY5Y cells Concentration: 5 μM Incubation Time: For 24 hours Result: Induced Autophagy. Cell Viability Assay[1] Cell Line: SH-SY5Y cells Concentration: 0.5, 5, 50 μM Incubation Time: For 24 hours Result: Could partially reverse MPP+-induced cell death, which was determined by enhancing cell viability. Western Blot Analysis[1] Cell Line: SH-SY5Y cells Concentration: 5 μM Incubation Time: 6, 12, 24, 36 hours Result: Time-dependently elevated the expression levels of LC3-II (a key marker of autophagy), Beclin-1, and its phosphorylation status, whereas reduced the level of the selective autophagy substrate SQSTM1/p62.
[In Vivo]
BL-918 (20, 40, or 80 mg/kg/day; oral gavage; began 2 days before the first injection of saline/MPTP and continuously maintained for 5 days after the last injection of saline/MPTP) attenuates the loss of DA and its metabolites. BL-918 obviously decreases the levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA)[1]. Animal Model: Male C57BL/6 mice (eight-week old) weighing between 20 and 25 g[1] Dosage: 20, 40, or 80 mg/kg Administration: Oral gavage; daily; began 2 days before the first injection of saline/MPTP and continuously maintained for 5 days after the last injection of saline/MPTP Result: Attenuated the loss of DA and its metabolites.
[References]
Chemical & Physical Properties
[ Density]:
1.5±0.1 g/cm3
[ Molecular Formula ]:
C23H15F8N3OS
[ Molecular Weight ]:
533.437
[ Exact Mass ]:
533.080811
[ LogP ]:
6.85
[ Index of Refraction ]:
1.592
Safety Information
[ Hazard Codes ]:
Xn