|MHY1485 | CAS#326914-06-1 | mTOR activator

MHY1485
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 406654

CAS#: 326914-06-1

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 ).

Chemical Structure

MHY1485

CAS# 326914-06-1

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 406654
Name: MHY1485
CAS#: 326914-06-1
Chemical Formula: C17H21N7O4
Exact Mass: 387.17
Molecular Weight: 387.400
Elemental Analysis: C, 52.71; H, 5.46; N, 25.31; O, 16.52

Price and Availability

Size	Price	Availability
100mg	USD 750	2 weeks
200mg	USD 1350	2 weeks
500mg	USD 2250	2 weeks
1g	USD 3250	2 weeks
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

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-]

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Product Data:

Product Data

Instruction:

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Biological target:	MHY1485 is a potent cell-permeable mTOR activator that targets the ATP domain of mTOR.
In vitro activity:	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. Reference: PLoS One. 2012;7(8):e43418. https://pubmed.ncbi.nlm.nih.gov/22927967/
In vivo activity:	This study reports that treatment of ovaries from juvenile mice with an mTOR activator MHY1485 stimulated mTOR, S6K1 and rpS6 phosphorylation. Culturing ovaries for 4 days with MHY1485 increased ovarian explant weights and follicle development. In vivo studies further demonstrated that pre-incubation of these ovaries with MHY1485 for 2 days, followed by allo-grafting into kidney capsules of adult ovariectomized hosts for 5 days, led to marked increases in graft weights and promotion of follicle development. Reference: PLoS One. 2015 Feb 24;10(2):e0117769. https://pubmed.ncbi.nlm.nih.gov/25710488/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMF	5.0	12.91
	DMSO	6.1	15.65

Preparing Stock Solutions

The following data is based on the product molecular weight 387.40 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:	1. Zhou J, Yao W, Li C, Wu W, Li Q, Liu H. Administration of follicle-stimulating hormone induces autophagy via upregulation of HIF-1α in mouse granulosa cells. Cell Death Dis. 2017 Aug 17;8(8):e3001. doi: 10.1038/cddis.2017.371. PMID: 28817115; PMCID: PMC5596559. 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. PMID: 22927967; PMCID: PMC3425474. 3. Liu P, Li M, Wu W, Liu A, Hu H, Liu Q, Yi C. Protective effect of omega-3 polyunsaturated fatty acids on sepsis via the AMPK/mTOR pathway. Pharm Biol. 2023 Dec;61(1):306-315. doi: 10.1080/13880209.2023.2168018. PMID: 36694426; PMCID: PMC9879202. 4. 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. PMID: 25710488; PMCID: PMC4340052.
In vitro protocol:	1. Zhou J, Yao W, Li C, Wu W, Li Q, Liu H. Administration of follicle-stimulating hormone induces autophagy via upregulation of HIF-1α in mouse granulosa cells. Cell Death Dis. 2017 Aug 17;8(8):e3001. doi: 10.1038/cddis.2017.371. PMID: 28817115; PMCID: PMC5596559. 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. PMID: 22927967; PMCID: PMC3425474.
In vivo protocol:	1. Liu P, Li M, Wu W, Liu A, Hu H, Liu Q, Yi C. Protective effect of omega-3 polyunsaturated fatty acids on sepsis via the AMPK/mTOR pathway. Pharm Biol. 2023 Dec;61(1):306-315. doi: 10.1080/13880209.2023.2168018. PMID: 36694426; PMCID: PMC9879202. 2. 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. PMID: 25710488; PMCID: PMC4340052.

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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.

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