MSDC 0160 (CAY10415) is a prototype mTOT-modulating insulin sensitizer being used in trials studying the treatment of Type 2 Diabetes and Alzheimer's Disease.

In the KKAy mouse model of diabetes, MSDC-0160 (100 mg/kg, p.o.) significantly enhanced insulin sensitivity by substantially reducing the levels of insulin and glucose in the circulatory system.

Within the insulin and IGF-1 signaling pathways, MSDC-0160 reduces resistance and restores IGF-1-induced phosphorylation of AKt and GSK-3. When used in conjunction with IGF-1 and 8 mM glucose, MSDC-0160 boosts the expression of specific genes within β-cells, including insulin, pdx1, nkx6.1, and nkx2.2, while maintaining insulin content without affecting glucose-induced insulin secretion. Additionally, MSDC-0160 promotes the differentiation of human β-cells and decreases the expression of apoptosis markers.

Measurement of activities of autophosphorylated/non-autophosphorylate CaMKII: CaMKII activity is measured utilizing syntideII as a substrate. Purified CaMKII is pre-incubated in the assay mixture ( 35 mM Hepes-Na ( pH 8.0 ), 10 mM MgC12, 0.5 μM CaM, 5 μM ATP, 1 mM CaCl2 or 1 mM EGTA, total 25 μL) at 30 °C for 2 minutes. After this pre-incubation, the protein substrate/radioactive ATP mixture is added to the same test tube and the preparation is further incubated at 30 °C, for 5 minutes ( final assay condition; 35 mM Hepes-Na (pH 8.0), 10 mM MgCl2, 0.125 μM CaCl2, 20 μM syntideII, 11.25 μM [ γ-32P] ATP, 10 % DMSO and indicated concentrations of KN-93, supplemented with 0.25 mM CaCl2 and 2 mM EGTA (for autophosphorylated samples) or 0.25 mM EGTA and 2 mM CaCl2 (for nonautophosphorylated samples ), total 100 μL ). The reaction is terminated by adding of 25 μL of 100 % ( w/v ) ice-cold TCA. After centrifugation, 80 μL of the supernatant is applied to phosphocellulose paper. The filters are then washed with 75 mM H3P04 for 15 min with continuous agitation. After 4-cycles of washing, the radioactivity retains on the filter paper is quantified in a liquid scintillation counter.