MHY1485 Chemical Properties

Melting point:

256-259 °C

Boiling point:

643.3±65.0 °C(Predicted)

Density 

1.415±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

DMSO: soluble2mg/mL, clear (warmed)

pka

6.19±0.10(Predicted)

form 

powder

color 

white to beige

Stability:

Stable for 1 year from date of purchase as supplied. Solutions in DMSO or DMF may be stored at -20°C for up to 3 months.

InChI

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)

InChIKey

MSSXBKQZZINCRI-UHFFFAOYSA-N

SMILES

N1=C(N2CCOCC2)N=C(N2CCOCC2)N=C1NC1=CC=C([N+]([O-])=O)C=C1

Safety Information

WGK Germany 

3

HS Code 

2934.99.3900

Storage Class

11 - Combustible Solids

MHY1485 Usage And Synthesis

Description

MHY1485 is a cell-permeable activator of mTOR that has been shown to increase levels of cellular mTOR Ser²⁴⁴⁸ and downstream substrate 4E-BP Thr^37/46 phosphorylation in rat liver Ac2F cells. It can induce cellular LC3-II accumulation in Ac2F cells and has been shown to inhibit autophagy by suppressing the fusion between autophagosomes and lysosomes.

Uses

MHY1485 has been used:

• to study the effect of mammalian target of rapamycin mTOR signalling on in vitro O-GlcNAcylation
• to inhibit autophagy
• as a mTOR agonist to demonstrate that the O-linked N-acetylglucosamine transferase- RNA helicase p68 (OGT-DDX5) axis regulates colorectal cancer cell proliferation and metastasis

Biochem/physiol Actions

MHY1485 is mTOR activator that potently inhibits autophagy by suppression of fusion between autophagosomes and lysosomes.

in vivo

IC 50

mTORC1; mTORC2; Autophagy

Background

MHY1485 is a small, synthetic compound that activates the molecular mammalian target of rapamycin. mTOR is a Ser/Thr protein kinase that functions as an ATP and amino acid sensor to balance nutrient availability and cell growth. Cellular mTOR is a core component of both mTORC1 and mTORC2 multiprotein complexes, which regulate cell growth, proliferation, motility, and survival, as well as transcription, protein synthesis, and autophagy. Treatment of rat hepatocytes with MHY1485 suppressed autophagy by activating mTOR and inhibiting the fusion of autophagosomes and lysosomes. MHY1485 activated the mTOR-Nrf2 signaling pathway in UV-treated skin cells, preventing cell death and apoptosis. The mTOR activator suppressed UV-induced reactive oxygen species production and DNA single-strand breaks in UV-treated skin keratinocytes and fibroblasts. Similar treatment with MHY1485 rescued cultured osteoblasts from the cytotoxic effects of dexamethasone exposure, and increased ovarian weights, restored endocrine function, and promoted primordial follicle development in mice.

References

[1] YEON JA CHOI. Inhibitory effect of mTOR activator MHY1485 on autophagy: suppression of lysosomal fusion.[J]. PLoS ONE, 2012: e43418. DOI:10.1371/journal.pone.0043418
[2] YUAN CHENG. Promotion of ovarian follicle growth following mTOR activation: synergistic effects of AKT stimulators.[J]. PLoS ONE, 2015: e0117769. DOI:10.1371/journal.pone.0117769
[3] SAI ZHAO . MHY1485 activates mTOR and protects osteoblasts from dexamethasone[J]. Biochemical and biophysical research communications, 2016, 481 3: Pages 212-218. DOI:10.1016/j.bbrc.2016.10.104
[4] BO YANG. MHY1485 ameliorates UV-induced skin cell damages via activating mTOR-Nrf2 signaling[J]. Oncotarget, 2017, 8 1: 12775-12783. DOI:10.18632/oncotarget.14299
[5] CAIXIA LI  Helmy M S. (Pro)renin receptor regulates autophagy and apoptosis in podocytes exposed to high glucose.[J]. American journal of physiology. Endocrinology and metabolism, 2015, 309 3: E302-10. DOI:10.1152/ajpendo.00603.2014

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