MHY1485

Biological Activity

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. MHY1485 treatment increases ribosomal protein S6 kinase (S6K) and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) phosphorylation, which are downstream targets of mTOR complex 1 (mTORC1), but decreases phosphorylation of Akt on mTOR complex 2 (mTORC2) target site serine 473.

Product Citations

• 

  Life Sci. 2020 Jun 15;251:117595.

  The in vitro effects of phospholipase D1-mTOR axis in liver fibrogenesis
  MHY1485 purchased from AbMole

• 

  Fish Shellfish Immunol. 2020 Jul;102:480-488.

  Target of rapamycin signaling inhibits autophagy in sea cucumber Apostichopus japonicus
  MHY1485 purchased from AbMole

Customer Product Validations & Biological Datas

	Source	Life Sciences (2020 Jun). Figure 5. MHY1485 (Abmole Bioscience, US)
	Method	Proliferation analysis by CCK-8 method
	Cell Lines	Rat HSCs cell line
	Concentrations	5 μM
	Incubation Time	48 h
	Results	Moreover, both PLD1-I and PLD1-SiRNA could significantly blunt proliferation of HSC-T6 treated with MHY1485 (mTOR activator)

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information

References

[1] Jilong Zhou, et al. Cell Death Dis. Administration of follicle-stimulating hormone induces autophagy via upregulation of HIF-1α in mouse granulosa cells

[2] Cheng Y, et al. PLoS One. Promotion of ovarian follicle growth following mTOR activation: synergistic effects of AKT stimulators.

[3] Choi YJ, et al. PLoS One. Inhibitory effect of mTOR activator MHY1485 on autophagy: suppression of lysosomal fusion.