product name Dimesna
Description: Dimesna (also called BNP-7787) is an uroprotective agent used to decrease urotoxicity caused by anticancer drugs such cisplatin. 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. 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.
References: Mol Cancer Ther. 2010 Sep;9(9):2558-67; Cancer Chemother Pharmacol. 2010 Apr;65(5):941-51.
326.34
Formula
C4H8Na2O6S4
CAS No.
16208-51-8
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 65 mg/mL (199.2 mM)
Water: 65 mg/mL (199.2 mM)
Ethanol: <1 mg/mL
Solubility (In vivo)
Saline: 30 mg/mL
Synonyms
BNP-7787
other peoduct :
| In Vitro |
In vitro activity: 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. 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. 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. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | Tumors of urinary bladder induced by cyclophosphamide (CP) in rats can be significantly reduced by Dimesna administration in a dose-related manner. |
| Animal model | CP treated Sprague-Dawley rats |
| Formulation & Dosage | Dissolved in drinking water; 12 or 35 mg/kg ; Oral administration |
| References | Mol Cancer Ther. 2010 Sep;9(9):2558-67; Cancer Chemother Pharmacol. 2010 Apr;65(5):941-51; Cancer. 1983 Feb 15;51(4):606-9. |
