Background:

Dimesna is an inhibitor of OAT family with IC50 value of 636 μM, 390 μM, and 590 μM for OAT1, OAT3, and OAT4, respectively [1].
OATs (organic anion transporters) involve in many life processes, like elimination of a variety of endogenous substances, xenobiotics and their metabolites from the body. It has been shown that OATs play an important role in mediating the renal and hepatic elimination of organic anions using molecular cloning method [2].
Dimesna is an OAT inhibitor and often used as an uroprotective drug. When tested with renal tubular cell line LLC-PK1, in combination with IF metabolites, dimesna treatment exerted uroprotective action [3]. When tested with human renal proximal tubule HK-2 cells, dimesna was detected to accumulate in cells and played an important role in reducing chemotherapy-induced toxicities [4].
参考文献:
[1].Cutler, M.J., et al., In vitro and in vivo assessment of renal drug transporters in the disposition of mesna and dimesna. J Clin Pharmacol, 2012. 52(4): p. 530-42.
[2].Roth, M., A. Obaidat, and B. Hagenbuch, OATPs, OATs and OCTs: the organic anion and cation transporters of the SLCO and SLC22A gene superfamilies. Br J Pharmacol, 2012. 165(5): p. 1260-87.
[3].Mohrmann, M., et al., Dithio-bis-mercaptoethanesulphonate (DIMESNA) does not prevent cellular damage by metabolites of ifosfamide and cyclophosphamide in LLC-PK1 cells. Pediatr Nephrol, 1994. 8(4): p. 458-65.
[4].Hausheer, F.H., et al., Accumulation of BNP7787 in human renal proximal tubule cells. J Pharm Sci, 2011. 100(9): p. 3977-84.