SGK1-IN-7

SGK1-IN-7 is an SGK1 inhibitor capable of crossing the blood-brain barrier, with an IC50 of 0.72 μM. It reduces the phosphorylation levels of TAU protein at Ser396 and Ser214 epitopes and exhibits antagonistic effects against Okadaic acid-induced toxicity. SGK1-IN-7 is applicable in Alzheimer's disease research.

SGK1-IN-7 (Compound 102) is a compound with low mutagenicity and cardiac safety risk, showing no significant inhibitory effects on hERG or Nav1.5 channels, and only moderate inhibition of the Cav1.2 channel (IC50 = 12.1 μM) at concentrations ranging from 6.25 to 50 μM over 30 minutes. At a concentration of 5 μM for 24 hours, SGK1-IN-7 exhibits significant neuroprotective effects on SH-SY5Y human neuroblastoma cells treated with Okadaic acid. Additionally, at the same concentration and duration, it significantly reduces phosphorylation levels of tau protein at Ser396 and Ser214 in SH-SY5Y cells without altering the total tau protein expression.

SGK1-IN-7 (Compound 102) demonstrates dose-dependent levels of plasma and brain exposure in male BALB/c mice when administered through intravenous injection, intraperitoneal injection, or oral dosing at 2.5-10 mg/kg. The brain-plasma ratios (brain-Kp) for a single dose were 0.49, 0.18, and 0.25, respectively, for each mode of administration.