CAIX/VEGFR-2-IN-2 (compound 5e) is a dual-target inhibitor with potent inhibitory effects on CAIX (KI=3.1 μM) and VEGFR-2 (IC50=32.1 nM). This compound is applicable in research involving pancreatic cancer (PANC1), breast cancer (MCF7), and prostate cancer cells (PC3).

VEGFR2:32.1 nM, CA IX:3.1 μM (Ki)

CA IX/VEGFR-2-IN-2 (compound 5e) exhibits selective activity against tumor cells in the order of PANC1, MCF7, and PC3, and significantly reduces PANC1 cell migration. In pancreatic cancer cells, it induces apoptosis by upregulating p53, BAX, cytochrome C, and caspases 3, 8, and 9, while downregulating Bcl-2 gene expression. The compound inhibits HIF-1α expression, reducing its concentration from 6.1±0.13 ng/mL to 3.7±0.09 ng/mL, achieving over a 1.5-fold suppression in PANC1 cells. It also causes an abnormal increase in ROS formation, leading to cell cycle arrest or apoptosis in PANC1 cells.

CA IX/VEGFR-2-IN-2 (compound 5e) administered intraperitoneally at doses of 5 and 10 mg/kg over two weeks in female Swiss albino mice demonstrates superior efficacy in reducing tumor volume and weight compared to the standard drug DOX at 10 mg/kg. The same dosing of CA IX/VEGFR-2-IN-2 results in further decreases in VEGF, MMP-2, and MMP-9 concentrations. Additionally, a 5 mg/kg dose leads to necrosis with scattered tumor cells, while a 10 mg/kg dose significantly mitigates diffuse and extensive necrosis, with a substantial reduction in tumor cell presence, indicating effective suppression of viable tumor cells.