sodium 2-({2-[(sodiooxy)sulfonyl]ethyl}disulfanyl)ethane-1-sulfonate

• ChemBase ID: 72470
• Molecular Formular: C4H8Na2O6S4
• Molecular Mass: 326.34226
• Monoisotopic Mass: 325.89991054
• SMILES: S(=O)(=O)(CCSSCCS(=O)(=O)O[Na])O[Na]
• Canonical SMILES: [Na]OS(=O)(=O)CCSSCCS(=O)(=O)O[Na]
• InChI: InChI=1S/C4H10O6S4.2Na/c5-13(6,7)3-1-11-12-2-4-14(8,9)10;;/h1-4H2,(H,5,6,7)(H,8,9,10);;/q;2*+1/p-2
• InChIKey: KQYGMURBTJPBPQ-UHFFFAOYSA-L

NAMES AND DATABASE IDS

Names

• IUPAC name: sodium 2-({2-[(sodiooxy)sulfonyl]ethyl}disulfanyl)ethane-1-sulfonate
• IUPAC Traditional name: sodium 2-{[2-(sodiooxysulfonyl)ethyl]disulfanyl}ethanesulfonate
• Synonyms: BNP7787; Tavocept; BioNumerik; Dimesna

Database IDs

• CAS Number: 16208-51-8
• PubChem SID: 162037395
• PubChem CID: 46931005

CALCULATED PROPERTIES

• H Acceptors: 4
• H Donor: 0
• LogD (pH = 5.5): 0.3066
• LogD (pH = 7.4): 0.3066
• Log P: 0.3066
• Molar Refractivity: 54.2562 cm^3
• Polarizability: 27.644495 Å^3
• Polar Surface Area: 86.74 Å^2
• Rotatable Bonds: 9
• Lipinski's Rule of Five: true

PROPERTIES

Safety Information

• Storage Condition: -20°C

Product Information

• Salt Data: Free Base

DETAILS

Selleck Chemicals - S1201

Research Area

• Description: Cancer

Biological Activity

• Description: Dimesna is an uroprotective agent used to decrease urotoxicity.
• 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 K_M 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]
• Clinical Trials: Dimesna is now in phase III clinical trial in patients with newly diagnosed or relapsed advanced primary adenocarcinoma of the lung treated with docetaxel or paclitaxel plus cisplatin.

Protocol

• Protocol: Kinase Assay ^[2]
• Fluorometric APN Assay: The activity of human APN is determined based on enzyme-specific fluorometric biochemical assays described as follows. The assay monitored the release of fluorescent product, free AMC, that is liberated when human APN cleaves Leu-AMC. Reaction conditionsdescribed herein used a vast excess of Leu-AMC (100 μM/ assay) in comparison with APN enzyme (~1.9 nM/assay or ~20 ng/assay) in each assay. The initial velocity in reactions is determined during the linear phase of the assay when substrate concentration is saturating (for each experiment calculating the rate of the reaction during the 2–8 minutes range of the assay). Additionally, the progress curve of the assays is monitored for at least 30 minutes. These assays are run in replicates of 6–8 per plate per test article concentration. For each test article, all assays are conducted on at least 2 different days to ensure reproducibility and quality of the data. Master mixes (75 μL total volume) containing substrate, test article and buffer are aliquoted to wells and plates are equilibrated to 37 °C for 5 minutes inside the Xuorimeter. It should be noted that deviations in plate equilibration can lead to lags that are reflected in nonlinear behavior during the initial portion of the enzyme progress curve. Next, twenty-five microliters (25 μL) of diluted human APN (8 × 10^4 μg/μL made by diluting 2 μL of 10 μg APN stock from R&D Systems with 1.47 mL of buffer) is added to individual wells to initiate the reaction (no enzyme controls are “initiated” with 25 μL of buffer only) and after addition of APN to equilibrated plates, plates are agitated in the Xuorimeter for 10 seconds prior to the first read. Buffer background control, enzyme only negative control, substrate autohydrolysis control, product only control (AMC) and enzyme activity positive control are also performed. Experiments where assays are initiated with Leu-AMCinstead of APN are also conducted for several test articles and give essentially identical results to the assays initiated with APN.
• Protocol: Animal Study ^[4]
• Animal Models: CP treated Sprague-Dawley rats
• Formulation: Mixed with the drinking water
• Doses: 12 or 35 mg/kg
• Administration: Orally five times a week

References

• References: [1] Parker AR, et al. Mol, Cancer Ther, 2010, 9(9), 2558-2567.
• References: [2] Hausheer FH, et al. Cancer Chemother Pharmacol, 2010, 65(5), 941-951.
• References: [3] Cutler MJ, et al. J Clin Pharmacol, 2012, 52(4), 530-542.
• References: [4] Habs MR, et al. Cancer, 1983, 51(4), 606-609.

REFERENCES

• Parker AR, et al. Mol, Cancer Ther, 2010, 9(9), 2558-2567.
• Hausheer FH, et al. Cancer Chemother Pharmacol, 2010, 65(5), 941-951.
• Cutler MJ, et al. J Clin Pharmacol, 2012, 52(4), 530-542.
• Habs MR, et al. Cancer, 1983, 51(4), 606-609.