BL-918

BL-918 is an orally active UNC-51-like kinase 1 (ULK1) activator with an EC₅₀ of 24.14 nM. BL-918 exerts its cytoprotective autophagic effect by targeting ULK complex. BL-918 has the potential for Parkinson’s disease (PD) treatment^[1]. In Vitro: BL-918 (compound 33i) binds to ULK1 with a high binding affinity (K_D=0.719 μM)^[1].
BL-918 (5 μM; for 24 hours) induces autophagy in Neuron-Like SH-SY5Y 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].
In Vivo: BL-918 (compound 33i; 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].