BL-918

Cas No.:	2101517-69-3
Chemical Name:	(R)-2-(3-(3,5-Bis(trifluoromethyl)phenyl)thioureido)-N-(2,4-difluorophenyl)-2-phenylacetamide
Synonyms:	BL918；BL 918；BL-918
SMILES:	O=C([C@@H](C1C=CC=CC=1)NC(=S)NC1C=C(C(F)(F)F)C=C(C(F)(F)F)C=1)NC1C(F)=CC(F)=CC=1
Formula:	C23H15F8N3Os
M.Wt:	533.44
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO
Publication:	[1]. Ouyang L, et al. Small-Molecule Activator of UNC-51-Like Kinase 1 (ULK1) That Induces Cytoprotective Autophagy for Parkinson's Disease Treatment. J Med Chem. 2018 Apr 12;61(7):2776-2792.

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.
Target:	ULK1:24.14 nM (EC50)
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.
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.
References:	[1]. Ouyang L, et al. Small-Molecule Activator of UNC-51-Like Kinase 1 (ULK1) That Induces Cytoprotective Autophagy for Parkinson's Disease Treatment. J Med Chem. 2018 Apr 12;61(7):2776-2792.