SIRT3 activator2 (compound 2a) acts as an activator of SIRT3. It is presumed to bind directly with SIRT3 in SH-SY5Y cells, as inferred through thermal stability, facilitating the SIRT3-dependent clearance of α-Syn. Furthermore, SIRT3 activator2 enhances motor functions in Parkinsonian mice and dose-dependently prevents the loss of dopaminergic (DA) neurons in the substantia nigra.

SIRT3 activator 2, at concentrations of 10 μM and 100 μM, functions as an activator of SIRT3. In SH-SY5Y cells, treatment with SIRT3 activator 2 (10 μM for 24 hours) enhances the thermal stability of SIRT3 (CETSA), indicating direct binding to SIRT3 (wb). Additionally, SIRT3 activator 2 (10 μM; 24h) facilitates the degradation of α-Syn through a SIRT3-dependent mechanism in SH-SY5Y cells, thereby offering neuroprotective effects (wb).

SIRT3 activator 2, administered intravenously at doses of 10, 20, and 40 mg/kg (Once per session; 24 days), enhances motor function in Parkinsonian mice induced by overexpression of α-synuclein. Additionally, SIRT3 activator 2, delivered via intracerebral microinjection at the same dosages, dose-dependently prevents the loss of substantia nigra DA neurons caused by overexpression of α-synuclein.