3-TYP

3-TYP inhibit SIRT3 with an IC50 of 16 nM, and is more potent over SIRT1 and SIRT2 with IC50 of 88 nM and 92 nM, respectively.^[1]

In vitro, with 50 μM 3-TYP abrogated the barrier protective effect of PD in multiple organs of septic mice. In HUVECs, 3-TYP (50 μM) diminished PD-mediated protection against F-actin redistribution, cadherin–catenin complex dissociation, and endothelial monolayer hyperpermeability.^[3] In vitro study it demonstrated that at 100 µM, 3-TYP decreased expression of genes involved in lipolysis and glucose transport GLUT4 compared to HNK. At the meantime, 3-TYP also caused an increase in gene expression of adipocyte-specific cytokines, including IL6, resistin, and TNF-α. In vitro, treatment with 100 µM 3-TYP obviously inhibited glucose uptake in 3T3-L1 adipocytes in contrast to control in the presence of insulin.^[5] In A/R-treated H9c2 cells, 4-P-PDOT (10 μM) and 3-TYP (5 μM) treatment resulted in no notable difference in cell viability. In addition, combination wiith 4-P-PDOT and 3-TYP elevated apoptotic signaling by increasing cleaved caspase-3 and Bax expression while decreasing Bcl-2 expression compared with that in the A/R + Mel group.^[6]

In vivo experiment it suggested that treatment with 50 mgkg intraperitoneally 3-TYP reversed the induction of mitophagy by decreasing the expression levels of FOXO3α, BINP3, LC3-II/LC3-I, SOD2, PRDX3, and P62.^[2] In vivo efficacy test it indicated that C57BL/6 mice were administrated 50 mg/kg 3-TYP abolished TBM's antioxidative effects.^[4]

References:
[1].Pi H, et al. SIRT3-SOD2-mROS-dependent autophagy in cadmium-induced hepatotoxicity and salvage by melatonin. Autophagy. 2015;11(7):1037-51.
[2].Yu W, et al. Dexmedetomidine Ameliorates Hippocampus Injury and Cognitive Dysfunction Induced by Hepatic Ischemia/Reperfusion by Activating SIRT3-Mediated Mitophagy and Inhibiting Activation of the NLRP3 Inflammasome in Young Rats. Oxid Med Cell Longev. 2020 Nov 20;2020:7385458.
[3].Wu J, et al. Polydatin protects against lipopolysaccharide-induced endothelial barrier disruption via SIRT3 activation. Lab Invest. 2020 Apr;100(4):643-656.
[4].Lv D, et al. Tubeimoside I Ameliorates Myocardial Ischemia-Reperfusion Injury through SIRT3-Dependent Regulation of Oxidative Stress and Apoptosis. Oxid Med Cell Longev. 2021 Nov 9;2021:5577019.
[5]. Lee AY, et al. Sirt3 Pharmacologically Promotes Insulin Sensitivity through PI3/AKT/mTOR and Their Downstream Pathway in Adipocytes. Int J Mol Sci. 2022 Mar 29;23(7):3740.
[6].Wu J, et al. Melatonin Attenuates Anoxia/Reoxygenation Injury by Inhibiting Excessive Mitophagy Through the MT2/SIRT3/FoxO3a Signaling Pathway in H9c2 Cells. Drug Des Devel Ther. 2020 May 25;14:2047-2060.