Biological Activity
ly335979 is a selective inhibitor of p-gp with ic50 value of 1.2 nm [1, 2].p-gp (p-glycoprotein) is a member of atp-binding cassette (abc) transporters and plays a pivotal role in pumping many foreign substances out of cells. it has been reported that abnormal expression of p-gp is correlated with the multidrug resistance of tumor cells [3].ly335979 is a potent p-gp inhibitor and has a different selectivity with the reported p-gp inhibitor cyclosporin a or verapamil. in drug-resistant cell line hl60/vcr with highly expression of p-gp, ly335979 exhibited highly restore ability of p-gp than cyclosporin a or verapamil and the ic 50 value of 1.2 nm [1]. when tested with a panel of cell lines over-expressed p-gp (cem/vlb100, mcf-7/adr, 2780ad, p388/adr, and ucla-p3.003vlb), administration of ly335979 reversed the cells resistance to vinblastine, doxorubicin, btoposide and taxol by inhibiting p-gp activity [2].in female nude mice model with ucla-p3.003vlb mdr tumor cells subcutaneous xenograft, pre-treated with ly335979 (30mg/kg) restored tumor cells sensitivity to taxol (20 mg/kg) which combination markedly suppressed solid tumor growth compared with control group [2].
References
1. green, l.j., p. marder, and c.a. slapak, modulation by ly335979 of p-glycoprotein function in multidrug-resistant cell lines and human natural killer cells. biochem pharmacol, 2001. 61(11): p. 1393-9.2. dantzig, a.h., et al., reversal of p-glycoprotein-mediated multidrug resistance by a potent cyclopropyldibenzosuberane modulator, ly335979. cancer res, 1996. 56(18): p. 4171-9.3. hu, t., et al., reversal of p-glycoprotein (p-gp) mediated multidrug resistance in colon cancer cells by cryptotanshinone and dihydrotanshinone of salvia miltiorrhiza. phytomedicine, 2014. 21(11): p. 1264-72.
