Dofequidar fuMarate

Uses

Dofequidar fumarate (MS-209) is an orally active quinoline compoundthat blocks P-glycoprotein (P-gp) and multidrug resistance-associated protein-1 (MDR-1). Dofequidar fumarate has highly potent reversing effect on multidrug-resistant tumor cells. Dofequidar fumarate competitively inhibits ABCB1/P-gp, ABCC1/MRP-1, blocks the efflux of chemotherapeutic agents, increases the drug concentration in cancer cells, and enhances the chemotherapeutic effect[1][2].

Biological Activity

dofequidar fumarate is a multidrug-resistant (mdr) - reversal agent [1].dofequidar fumarate is a quinoline derivative and has highly potent reversing effect on multidrug-resistant tumor cells. it prevents the transport of antitumor drugs through interacting with the drug-efflux pump p-glycoprotein directly and thereby reverses mdr. in vincristine (vcr)-resistant p388/vcr cells and adriamycin (adm)- resistant p388/adm cells, dofequidar fumarate at 1μm and 3μm can completely reverse the drug resistance. it also shows significant effects on the mdr k562 cells. furthermore, in mice model bearing hct-15 xenografts, combination therapy of dofequidar fumarate and docetaxel induces remarkable tumor growth inhibition. dofequidar fumarate also shows significant reversing effect in mcf-7/adm-bearing mice [1, 2].

in vivo

References

[1] sato w, fukazawa n, nakanishi o, et al. reversal of multidrug resistance by a novel quinoline derivative, ms-209. cancer chemotherapy and pharmacology, 1995, 35(4): 271-277.
[2] naito m, matsuba y, sato s, et al. ms-209, a quinoline-type reversal agent, potentiates antitumor efficacy of docetaxel in multidrug-resistant solid tumor xenograft models. clinical cancer research, 2002, 8(2): 582-588.