TML-6, an oral curcumin derivative, demonstrates inhibitory effects on the synthesis of β-amyloid precursor protein and β-amyloid (Aβ). Additionally, TML-6 exhibits upregulation of Apo E, suppression of NF-κB and mTOR, and enhancement of the anti-oxidative Nrf2 gene activity. Considering its diverse pharmacological profile, TML-6 holds promise as a valuable research tool for investigating Alzheimer's disease (AD)[1].

TML-6 (0.65-5.24 μg/mL; for 24 h) reduces the protein expression levels of APP and phospho-NF-κB, and induces the protein expression level of ApoE. TML-6 inhibits the mTOR signaling pathway through the suppression of phospho-mTOR[1]. TML-6 (0.31, 0.63, 2.5, 5, 10, 20 μM; 24 h) reveals no cytotoxicity in Huh-7 cells at concentrations below 5 μM and has an IC50 of 4.19 μg/mL (8 μM)[1]. TML-6 (1.05, 2.09, 3.14, 4.19 μg/mL; 24 h) reduces the production of Aβ40 and Aβ42 between 1.05, 2.09 and 3.14 μg/mL (equal to 2, 4 and 6 μM) in a dose-dependent manner in N2a/APPswe cell[1]. TML-6 can exhibit transcriptional activation of the Nrf2 gene in a dose-dependent manner, with the highest activity at a concentration of 1.32 μg/mL[1].

TML-6 (diet; 150 mg/kg/day; for four months) significantly improves learn ng, suppresses the microglial activation marker Iba-1, and reduces Aβ in the brain[1]. TML-6 (oral; 150 mg/kg) exhibits a T1/2 of 1.27 hours, a Cmax of 35.9 ng/mL, and an AUC of 177 ng•hr/mL[1].