SBI-0206965 has been used to study its effect on the growth of cadmium-transformed prostate epithelial cells.[1]
Biochem/physiol Actions
SBI-0206965 is a potent and selective inhibitor of the serine/threonine autophagy-initiating kinases ULK1 and ULK2 with selectivity for ULK1.
SBI-0206965 is a potent and selective inhibitor of the serine/threonine autophagy-initiating kinases ULK1 and ULK2 with selectivity for ULK1. SBI-0206965 has an IC50 value of 108 nM for ULK1, compared to 711nM for ULK2. Tumor cells require autophagy to remove misfolded proteins or damaged cellular organelles. SBI-0206965 was shown to suppress autophagy induced by mTOR inhibition. mTOR signaling is often hyperactive in many tumors and can drive proliferation, so mTOR inhibitors are being investigated as anticancer agents. However, mTOR inhibition also results in activation of the ULK1-dependent autophagy survival response, and most results with mTOR inhibitors have been at best cytostatic. SBI-0206965 synergizes with mTOR inhibition to induce apoptosis and cell death.
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.
