AKR1B10-IN-1, a powerful AKR1B10 (Aldo-Keto Reductase 1B10) inhibitor, demonstrates an IC50 value of 3.5 nM. This compound effectively curtails the proliferation, metastasis, and Cisplatin (CDDP) resistance of lung cancer cells.

AKR1B10:3.5 nM , AKR1B1:277 nM

AKR1B10-IN-1 (compound 4e), at concentrations ranging from 0 to 20 μM over 96 hours, effectively inhibits the growth of both A549 and AKR1B10-stably overexpressing A549 cells (A549/1B10), demonstrating a potent ability to hinder cell proliferation attributed to both overexpressed and endogenous AKR1B10. Additionally, at concentrations up to 40 μM, with a 2-hour pre-treatment followed by a 24-hour incubation with cisplatin (CDDP), AKR1B10-IN-1 significantly reduces cell viability in cisplatin-resistant A549 cells (CDDP-R-A549) in a dose-responsive manner. Cell viability assays confirm these effects, showing a statistically significant suppression in A549 and A549/1B10 cell growth at 20 μM and a noticeable decrease in viability of CDDP-R-A549 cells, particularly at 40 μM, after pretreatment with AKR1B10-IN-1 followed by CDDP exposure.