PTP1B/AKR1B1-IN-1 is a dual inhibitor targeting protein tyrosine phosphatase 1B (PTP1B) and aldose reductase (AKR1B1), exhibiting inhibitory potency with IC50s of 0.06 μM for PTP1B and 4.3 μM for AKR1B1. Additionally, it inhibits T-cell protein tyrosine phosphatase (TC-PTP) with an IC50 of 9 μM. This compound acts as an insulin-mimetic in murine myoblasts and diminishes AKR1B1-mediated sorbitol accumulation, contributing to the management of blood glucose levels and the inhibition of type 2 diabetes mellitus (T2DM) development [1].

PTP1B/AKR1B1-IN-1 (化合物 6f) exhibits tight binding to PTP1B and AKR1B1 with K_i values of 4.6 μM and 0.08 μM, respectively. At a concentration of 20 μM over 24 hours, this compound demonstrates negligible cytotoxicity in differentiated murine C2C12 myoblasts [1]. It also enhances insulin (10 μM; 15 minutes)-stimulated increase in Akt phosphorylation in the C2C12 cell line at the same concentration and duration [1]. Furthermore, treatment with PTP1B/AKR1B1-IN-1 (2 μM; 24 hours) significantly impairs sorbitol accumulation in the human lens epithelial cell line B3 (HLE) when co-incubated with 75 mM D-glucose for 24 hours [1].