ULK1 (unc-51-like kinase 1), a serine/threonine protein kinase, is essential for the initial stages of autophagy and can be targeted to block autophagy for disease therapy[2]. MRT68921 hydrochloride is the most potent inhibitor of both ULK1 and ULK2, with greater than a 15-fold reduction in the IC50 for ULK1 (2.9 nM) and greater than a 30-fold reduction for ULK2 (1.1 nM)[2]. In line with the in vitro IC50 values, 1 μM MRT68921 was sufficient to reduce phospho-ATG13 which was used as a measure of ULK1 activity to control levels. Therefore, this compound could reduce ULK1 activity in cells. Importantly, it also blocked autophagy as indicated by LC3-II levels[2].
MRT68921 HCl 细胞实验
Cell Line
Concentration
Treated Time
Description
References
MEC-1 cells
10 µM
8 hours
Immunoblot analysis of p62/SQSTM1 levels confirmed venetoclax-induced autophagy in MEC-1 cells.
Cancers (Basel). 2021 Sep 10;13(18):4557
THP1-DiFluo hLC3 cells
1-25 µM
24 hours
Assessed autophagy flux induced by venetoclax, showing venetoclax triggered autophagy in a concentration-dependent manner.
Cancers (Basel). 2021 Sep 10;13(18):4557
Primary microglia
1, 10, or 30 µM
3 or 6 hours
To test the inhibitory effect of MRT68921 on autophagy, results showed that MRT68921 at 30 µM for 3 hours reduced autophagosome degradation, while at 10 µM for 6 hours it reduced both autophagosome formation and degradation.
Front Immunol. 2021 Jan 29;11:620602
MEC-1 cells
1 µM
24 hours
MRT68921 inhibited autophagy, leading to increased p62/SQSTM1 levels.
Cancers (Basel). 2021 Sep 10;13(18):4557
MOLM-13 SORE6+ cells
50-500 nM
24 hours
Inhibition of ULK1/2 activity significantly reduced the resistance of SORE6+ cells to Ara-C
Int J Mol Sci. 2024 Jan 4;25(1):646
LN229 cells
20 μM
5 hours
Inhibits ULK1 activity, blocks autophagy and induces apoptosis
J Cell Mol Med. 2022 Jul;26(14):3873-3890
MT330 cells
20 μM
5 hours
Inhibits ULK1 activity, blocks autophagy and induces apoptosis
J Cell Mol Med. 2022 Jul;26(14):3873-3890
mouse embryonic fibroblasts (MEFs)
1 μM
1 hour
To evaluate the inhibition of ULK1 activity by MRT68921 and its effect on autophagy. Results showed that MRT68921 significantly reduced phosphorylation of ATG13 at serine 318 and blocked autophagic flux.
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