SBI-0206965

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

SBI-0206965 (SBI 0206965) 是一种有效且特异性的小分子 ULK1 激酶抑制剂，IC50 为 108 nM。

SBI-0206965 (SBI 0206965) is a potent and specific small molecule ULK1 kinase inhibitor with IC50 of 108 nM; displays 7-fold less potency for ULK2 (IC50=711 nM); inhibits Beclin1 Ser15 and Vps34 Ser249 phosphorylation to comparable extents in HEK-293T cells; suppresses autophagy induced by mTOR inhibition and prevents ULK1-dependent cell survival; greatly synergized with mTOR inhibitors to kill tumor cells.

SBI-0206965 (5-20 μM; 24 hours) induces apoptosis of A498 and ACHN cells during starvation.SBI-0206965 (5-20 μM; 24 hours) attenuates the phosphorylation of Ser108 of the AMPK β1 subunit and increases the levels of cleaved Caspase 8 and PARP, markers of apoptosis. Apoptosis Analysis Cell Line:A498 and ACHN cells (starvation medium (EBSS) treatment) Concentration:5, 10 ,20 μM Incubation Time:24 hoursResult:Induced significant levels of apoptosis.Western Blot Analysis Cell Line:A498 and ACHN cells (EBSS treatment)Concentration:5, 10, 20?μMIncubation Time:24 hoursResult:Attenuated the phosphorylation of Ser108 of the AMPK β1 subunit and increased the levels of cleaved Caspase 8 and PARP, markers of apoptosis. Autophagy was evaluated by analysis of LC3B and p62.

SBI-0206965 (50?mg/kg; i.p.; once every 3 days for 37 days) inhibites tumour growth and induces apoptosis in A498 xenograft tumours. Animal Model:Six-week-old male BALB/c nude mice (A498 xenograft tumours)Dosage:50?mg/kg Administration:Intraperitoneal injection; once every three days for 37 days Result:Significantly suppressed tumour growth.

SBI 0206965 | SBI0206965

Autophagy

ULK

ULK1

Cancer

——

1884220-36-3

489.3192

C21H21BrN4O5

>98% (HPLC)

10 mM in DMSO

O=C(NC)C1=CC=CC=C1OC2=NC(NC3=CC(OC)=C(OC)C(OC)=C3)=NC=C2Br

2-((5-bromo-2-((3,4,5-trimethoxyphenyl)amino)pyrimidin-4-yl)oxy)-N-methylbenzamide

(-20℃)

With Ice Pack

≥ 2 years