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MedKoo CAT#: 406654
Description: MHY1485 is an mTOR activator that potently inhibits autophagy by suppression of fusion between autophagosomes and lysosomes. Autophagy is a major degradative process responsible for the disposal of cytoplasmic proteins and dysfunctional organelles via the lysosomal pathway. Treatment with MHY1485 suppressed the basal autophagic flux, and this inhibitory effect was clearly confirmed in cells under starvation, a strong physiological inducer of autophagy. The levels of p62 and beclin-1 did not show significant change after treatment with MHY1485. Decreased co-localization of autophagosomes and lysosomes in confocal microscopic images revealed the inhibitory effect of MHY1485 on lysosomal fusion during starvation-induced autophagy. These effects of MHY1485 led to the accumulation of LC3II and enlargement of the autophagosomes in a dose- and time-dependent manner. Furthermore, MHY1485 induced mTOR activation and correspondingly showed a higher docking score than PP242, a well-known ATP-competitive mTOR inhibitor, in docking simulation. In conclusion, MHY1485 has an inhibitory effect on the autophagic process by inhibition of fusion between autophagosomes and lysosomes leading to the accumulation of LC3II protein and enlarged autophagosomes. MHY1485 also induces mTOR activity, providing a possibility for another regulatory mechanism of autophagy by the MHY compound. The significance of this study is the finding of a novel inhibitor of autophagy with an mTOR activating effect. (copied from: PLoS One. 2012;7(8):e43418 ).
MedKoo Cat#: 406654
Chemical Formula: C17H21N7O4
Exact Mass: 387.1655
Molecular Weight: 387.39
Elemental Analysis: C, 52.71; H, 5.46; N, 25.31; O, 16.52
Synonym: MHY-1485; MHY1485; MHY 1485.
IUPAC/Chemical Name: 4,6-dimorpholino-N-(4-nitrophenyl)-1,3,5-triazin-2-amine
InChi Key: MSSXBKQZZINCRI-UHFFFAOYSA-N
InChi Code: InChI=1S/C17H21N7O4/c25-24(26)14-3-1-13(2-4-14)18-15-19-16(22-5-9-27-10-6-22)21-17(20-15)23-7-11-28-12-8-23/h1-4H,5-12H2,(H,18,19,20,21)
SMILES Code: O=[N+](C1=CC=C(NC2=NC(N3CCOCC3)=NC(N4CCOCC4)=N2)C=C1)[O-]
1: Cheng Y, Kim J, Li XX, Hsueh AJ. Promotion of ovarian follicle growth following mTOR activation: synergistic effects of AKT stimulators. PLoS One. 2015 Feb 24;10(2):e0117769. doi: 10.1371/journal.pone.0117769. eCollection 2015. PubMed PMID: 25710488; PubMed Central PMCID: PMC4340052.
2: Choi YJ, Park YJ, Park JY, Jeong HO, Kim DH, Ha YM, Kim JM, Song YM, Heo HS, Yu BP, Chun P, Moon HR, Chung HY. Inhibitory effect of mTOR activator MHY1485 on autophagy: suppression of lysosomal fusion. PLoS One. 2012;7(8):e43418. doi: 10.1371/journal.pone.0043418. Epub 2012 Aug 22. Erratum in: PLoS One. 2013;8(1). doi:10.1371/annotation/e3163ad5-f3d8-4a21-b3e1-f2033a76f9db. PubMed PMID: 22927967; PubMed Central PMCID: PMC3425474.