Dimesna  (Synonyms: BNP-7787)

Dimesna is an protective agent used to decrease urotoxicity. IC50 value: Target: in vitro: Dimesna modulates paclitaxel-induced hyperpolymerization of MTP in a dose-dependent manner, and mesna, an in vivo metabolite of Dimesna, protects against time-dependent cisplatin-induced inactivation of MTP. [1] Dimesna -mediated prevention or mitigation of cisplatin-induced nephrotoxicity may involve aminopeptidase N (APN) inhibition by certain Dimesna -derived esna-disulfide heteroconjugates and appears correlated to the presence of a glycinate moiety and/or an anionic group. Two general mechanisms for Dimesna -mediated nephroprotection of cisplatin-induced nephrotoxicity involving the gamma-glutamyl transpeptidase (GGT), APN and cysteine-conjugated-β-lyase (CCBL) nephrotoxigenic pathway are proposed which acting in a concerted and/or synergistic manner, and thereby prevent or mitigate cisplatin-induced renal toxicity. [2] Mesna and its dimer, Dimesna, are coadministered for mitigation of ifosfamide- and cisplatin-induced toxicities, respectively. Dimesna is selectively reduced to mesna in the kidney, producing its protective effects. In vitro screens of uptake and efflux transporters reveal renal organic anion transporters OAT1, OAT3, and OAT4 are responsible for kidney-specific uptake of Dimesna. Uptake of Dimesna by OAT1, OAT3, and OAT4 is determined to be saturable with KM of 636 μM, 390 μM and 590 μM, respectively. [3] in vivo: Tumors of urinary bladder induced by cyclophosphamide (CP) in rats can be significantly reduced by Dimesna administration in a dose-related manner. [4]

326.34

Solid

C₄H₈Na₂O₆S₄

16208-51-8

O=S(CCSSCCS(=O)(O[Na])=O)(O[Na])=O

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

• [1]. Parker AR, et al. BNP7787-mediated modulation of paclitaxel- and cisplatin-induced aberrant microtubule protein polymerization in vitro. Mol Cancer Ther. 2010 Sep;9(9):2558-2567.  [Content Brief]

  [2]. Hausheer FH, et al.Mechanistic study of BNP7787-mediated cisplatin nephroprotection: modulation of gamma-glutamyl transpeptidase. Cancer Chemother Pharmacol. 2010 Apr;65(5):941-951.  [Content Brief]

  [3]. Cutler MJ, et al. In vitro and in vivo assessment of renal drug transporters in the disposition of mesna and dimesna. J Clin Pharmacol. 2012 Apr;52(4):530-542.  [Content Brief]

  [4]. Habs MR,et al. Prevention of urinary bladder tumors in cyclophosphamide-treated rats by additional medication with the uroprotectors sodium 2-mercaptoethane sulfonate (mesna) and disodium 2,2'-dithio-bis-ethane sulfonate (dimesna). Cancer. 1983 Feb 15;51(4):606-609.  [Content Brief]