SBI-0206965 is identified as a potent and selective inhibitor of the autophagy kinase ULK1, showing cell permeability with an IC50 of 108 nM for ULK1 kinase. It also exhibits inhibition towards ULK2, although with lesser potency, having an IC50 of 711 nM[1].
体内研究
In vivo, a dose of 50 mg/kg of SBI-0206965, administered intraperitoneally once every three days for a duration of 37 days, effectively inhibits tumor growth and promotes apoptosis in A498 xenograft tumors, showcasing its therapeutic potential in cancer treatment[1].
体外研究
When administered at concentrations ranging from 5 to 20 μM for 24 hours, SBI-0206965 triggers apoptosis in A498 and ACHN cells under starvation conditions. This apoptotic induction is further evidenced by the attenuation of Ser108 phosphorylation on the AMPK β1 subunit alongside increased levels of cleaved Caspase 8 and PARP, which are established markers of apoptosis[1].
作用机制
SBI-0206965 occupies a pocket that partially overlaps the ATP active site in a type Iib inhibitor manner.
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