Dofequidar fumarate (MS-209)(MS-209 fumarate), a quinoline-based compound administered orally, is known for counteracting multidrug resistance (MDR) through the inhibition of ABCB1/P-glycoprotein (P-gp) and ABCC1/MDR-associated protein 1.

Dofequidar fumarate effectively overcomes docetaxel resistance in MDR cancer cells, and this concentration reaches> 7 h in plasma without severe toxicity.Dofequidar fumarate restored the chemical sensitivity of SBC-3/ADM cells to VP-16, ADM and VCR in a dose-dependent manner in vitro. Dofequidar inhibits the outflow of chemotherapy drugs and increases the sensitivity of anti-cancer drugs to CSC-like side population (SP) cells isolated from various cancer cell lines. Dofequidar treatment greatly reduces the number of cells in the SP component. In 4-1St cells with strong resistance to ADM and VCR, Dofequidar fumarate at a concentration of 3 microM increased the cytotoxicity of ADM and VCR by 88-fold and 350-fold, respectively.

Docetaxel alone at the maximum tolerated dose (MTD) has significant antitumor activity against intrinsically resistant HCT-15 tumor xenografts, while Dofequidar fumarate also enhances the antitumor effect of docetaxel active. For MCF-7/ADM tumor xenografts expressing large amounts of P-gp, docetaxel alone did not show antitumor activity at MTD, while the combination of MTD and Dofequidar fumarate for docetaxel greatly reduced MCF -7/ADM tumor growth. Intravenous injection of SBC-3 or SBC-3/ADM cells will produce metastatic colonies in the liver, kidneys, and lymph nodes in severe combined immunodeficiency (SCID) mice depleted by natural killer (NK) cells, although SBC-3/ ADM cells produce faster transfers than SBC-3 cells. The treatment of VP-16 and ADM reduced the formation of metastasis of SBC-3 cells, while the same treatment did not affect the metastasis of SBC-3/ADM cells. Although the use of MS-209 alone has no effect on the transfer of SBC-3 or SBC-3/ADM cells, the combined use of MS-209 and VP-16 or ADM can significantly inhibit the proliferation of SBC-3/ADM cells Metastasis to form an organ.