SBI-0206965

Description

ULK1 is a serine/threonine kinase that acts upstream of phosphatidylinositol 3-kinase (PI3K) to regulate the formation of autophagophores, the precursors of autophagosomes, in response to nutrient deprivation. It is activated by phosphorylation by AMPK and, in turn, phosphorylates and inhibits AMPK. SBI-0206965 is an inhibitor of ULK1 (IC₅₀ = 108 nM) that is less effective against ULK2 (IC₅₀ = 711 nM). It is selective for ULK1 and ULK2 over a panel of 456 additional kinases, showing activity against a few kinases in vitro but not in cells. SBI-0206965 suppresses autophagy induced by mTOR inhibition via AZD 8055 . It also blocks ULK1-dependent cell survival following nutrient deprivation.

The Uses of SBI-0206965

SBI-0206965 is an inhibitor of ULK1. It also blocks ULK1-dependent cell survival following nutrient deprivation. ULK1 is a serine/threonine kinase that acts upstream of phosphatidylinositol 3-kinase (PI3K) to regulate the formation of autophagophores, the precursors of autophagosomes, in response to nutrient deprivation.

Biochem/physiol Actions

Since most of the tumor cells survive on autophagy mechanism, inhibition of autophagy inducers Unc-51 (serine/threonine-protein kinase)-like autophagy activating kinase (ULK1 and ULK2) might be useful in cancer therapy.

References

1) Egan?et al. (2015), Small Molecules Inhibition of the Autophagy Kinase ULK1 and Identification of ULK1 Substrates; Mol. Cell, 59?285