LIB3S0280

LIB3S0280 is a potent TBK1 inhibitor with an IC₅₀ value of 493.9 nM. LIB3S0280 exhibits better anticancer effects in pancreatic cancer cell lines with high TBK1 expression. LIB3S0280 inhibits TBK1 downstream signaling pathways, including PI3K/AKT and NF-κB. LIB3S0280 induces G2/M arrest, apoptosis and cellular senescence. LIB3S0280 can be used for pancreatic ductal adenocarcinoma (PDAC) research ^[1].

In Vitro, LIB3S0280 (72-96 h) shows significant inhibition against high TBK1-expressing pancreatic cancer cell lines with the GI50 values of 2.24 μM (MIA PaCa-2) and 4.71 μM (PANC-1), and IC₅₀ values of 6.64 μM (MIA PaCa-2) and 10.98 μM (PANC-1) at 96 h^[1]. LIB3S0280 (10-20 μM, 3 h) inhibits TBK1 downstream signaling, including the PI3K/AKT and NF-κB pathways, by effectively reducing the phosphorylation of its key targets, AKT (Ser473) and IκBα, in MIA PaCa-2 and PANC-1 cells^[1]. LIB3S0280 (10-20 μM, 48-96 h) induces G₂/M arrest, apoptosis, and cellular senescence in pancreatic cancer cells (MIA PaCa-2 and PANC-1) by modulating key regulators like p-cdc2, p-MPM2, cyclin B1, and p21^[1].

References:
[1]. Wan-Hsi Shih, et al. Discovery of novel TANK-Binding Kinase 1 (TBK1) inhibitor against pancreatic ductal adenocarcinoma. Int J Biol Macromol. 2024 Dec;283(Pt 1):137296.