3-TYP

Biological Activity

3-TYP is a selective SIRT3 inhibitor with an IC50 value of 16 nM, which is more potent over SIRT1 and SIRT2. 3-TYP significantly attenuates melatonin-induced increases in deacetylated-SOD2 expression and SOD2 activity in HepG2 cells exposed to Cd.

In vivo, 3-TYP significantly decreases SIRT3 activity and increases the acetylation of SOD2 compared with that in the control group, without influencing SIRT3 expression. 3-TYP attenuates the cardioprotective effects of melatonin by decreasing the LVEF and LVFS after 24 hour of reperfusion. 3-TYP also increases the infarct size, serum LDH levels, and apoptotic ratio compared with those in the IR+Mel group.

Protocol

Cell Experiment
Cell lines	HepG2 cells
Preparation method	Cells are randomly divided into the following treatment groups: 10 μM Cd; melatonin (1 μM)+10 μM Cd; 3-TYP (50 μM)+10 μM Cd; and 3-TYP (50 μM)+melatonin (1 μM)+10 μM Cd. cells are treated for 12 h. The role of the SIRT3-SOD2 pathway in hepatic cell protection after melatonin pretreatment is investigated.
Concentrations	50 μM
Incubation time	12 h

Animal Experiment
Animal models	Sprague-Dawley rats
Formulation	ethanol (70%), propylene glycol (20%), NaHCO3 (10%)
Dosages	5 mg/kg
Administration	i.v.

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 resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 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 resveratrol of 11.2 mg/kg.

Chemical Information

References

Melatonin ameliorates myocardial ischemia reperfusion injury through SIRT3-dependent regulation of oxidative stress and apoptosis.
Zhai M, et al. J Pineal Res. 2017 Sep;63(2). PMID: 28500761.

Polydatin ameliorates injury to the small intestine induced by hemorrhagic shock via SIRT3 activation-mediated mitochondrial protection.
Zeng Z, et al. Expert Opin Ther Targets. 2016 Jun;20(6):645-52. PMID: 27067422.

SIRT3-SOD2-mROS-dependent autophagy in cadmium-induced hepatotoxicity and salvage by melatonin.
Pi H, et al. Autophagy. 2015;11(7):1037-51. PMID: 26120888.