mrt68921-free-base

Description: MRT-68921 is a novel, potent and dual inhibitor of the autophagy kinase ULK1 and ULK2 with IC50s of 2.9 and 1.1 nM, respectively. Autophagy is found to be a critical cell-degradative and protectiveprocess recycling damaged and long-lived cellular components. ULK1 is aserine/threonine protein kinase that is important for the initial stagesof autophagy. MRT68921 was identified to be relatively specific, but still couldinhibit a number of kinases by over 80%. Most importantly, TBK1/IKK aswell as the AMPK-related kinases were still found to be targeted.Moreover, by using LKB1 knock-out MEFs, it was found that LC3 flux wascomparable with matched, wild-type MEFs and could be inhibited to thesame extent in the treatment with MRT68921. Thus, these kinases aresuggested to be not the target of MRT68921 in blocking autophagy. Inaddition, MRT68921 was found to be able to block the WT-restored ATG13phosphorylation and autophagy, which was similar to cells expressingendogenous ULK1. In contrast, in cells expressing a similar level ofM92T ULK1, MRT68921 could not reduce either ATG13 phosphorylation or LC3flux, which indicated that MRT68921 was truly able to block autophagyvia ULK1 kinase inhibition.

References: Petherick KJ, Conway OJ, Mpamhanga C, Osborne SA, Kamal A, Saxty B, Ganley IG. Pharmacological inhibition of ULK1 kinase blocks mammalian target of rapamycin (mTOR)-dependent autophagy. J Biol Chem. 2015 May 1; 290(18):11376-83.

Related CAS #: 1190379-70-4 (free base) 2080306-21-2 (HCl)