MedKoo product information:

Dimesna

Dimesna is a synthetic derivative of dithio-ethane sulfonate with uroprotective properties. In the kidney, dimesna undergoes reduction to the free thiol compound, mesna, which reacts chemically with the urotoxic ifosfamide metabolites acrolein and 4-hydroxy-ifosfamide, resulting in their detoxification. This agent also inhibits cyclophosphamide-induced hemorrhagic cystitis. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Current developer:    Takeda Pharmaceutical Company Limited.

  1: Hausheer FH, Parker AR, Petluru PN, Jair KW, Chen S, Huang Q, Chen X, Ayala PY, Shanmugarajah D, Kochat H. Mechanistic study of BNP7787-mediated cisplatin nephroprotection: modulation of human aminopeptidase N. Cancer Chemother Pharmacol. 2010 May 4. [Epub ahead of print] PubMed PMID: 20440617.

2: Hausheer FH, Shanmugarajah D, Leverett BD, Chen X, Huang Q, Kochat H, Petluru PN, Parker AR. Mechanistic study of BNP7787-mediated cisplatin nephroprotection: modulation of gamma-glutamyl transpeptidase. Cancer Chemother Pharmacol. 2010 Apr;65(5):941-51. Epub 2009 Aug 28. PubMed PMID: 19714332.

3: Shanmugarajah D, Ding D, Huang Q, Chen X, Kochat H, Petluru PN, Ayala PY, Parker AR, Hausheer FH. Analysis of BNP7787 thiol-disulfide exchange reactions in phosphate buffer and human plasma using microscale electrochemical high performance liquid chromatography. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Apr 1;877(10):857-66. Epub 2009 Feb 28. PubMed PMID: 19278906.

4: Głowacki R, Gryglik D, Kuśmierek K, Bald E. Urinary mesna and total mesna measurement by high performance liquid chromatography with ultraviolet detection. Talanta. 2005 Apr 30;66(3):534-9. Epub 2005 Jan 1. PubMed PMID: 18970018.

5: Bastings MM, van Baal I, Meijer EW, Merkx M. One-step refolding and purification of disulfide-containing proteins with a C-terminal MESNA thioester. BMC Biotechnol. 2008 Oct 1;8:76. PubMed PMID: 18828922; PubMed Central PMCID: PMC2570673.

6: Miller AA, Wang XF, Gu L, Hoffman P, Khatri J, Dunphy F, Edelman MJ, Bolger M, Vokes EE, Green MR; Cancer and Leukemia Group B (CALGB). Phase II randomized study of dose-dense docetaxel and cisplatin every 2 weeks with pegfilgrastim and darbepoetin alfa with and without the chemoprotector BNP7787 in patients with advanced non-small cell lung cancer (CALGB 30303). J Thorac Oncol. 2008 Oct;3(10):1159-65. PubMed PMID: 18827613.

7: Wang And X, Guo Z. The role of sulfur in platinum anticancer chemotherapy. Anticancer Agents Med Chem. 2007 Jan;7(1):19-34. Review. PubMed PMID: 17266503.

8: Patzer L, Hernando N, Ziegler U, Beck-Schimmer B, Biber J, Murer H. Ifosfamide metabolites CAA, 4-OH-Ifo and Ifo-mustard reduce apical phosphate transport by changing NaPi-IIa in OK cells. Kidney Int. 2006 Nov;70(10):1725-34. Epub 2006 Sep 27. PubMed PMID: 17003823.

9: Boven E, Westerman M, van Groeningen CJ, Verschraagen M, Ruijter R, Zegers I, van der Vijgh WJ, Giaccone G. Phase I and pharmacokinetic study of the novel chemoprotector BNP7787 in combination with cisplatin and attempt to eliminate the hydration schedule. Br J Cancer. 2005 May 9;92(9):1636-43. PubMed PMID: 15841080; PubMed Central PMCID: PMC2362054.

10: Verschraagen M, Boven E, Torun E, Hausheer FH, Bast A, van der Vijgh WJ. Possible (enzymatic) routes and biological sites for metabolic reduction of BNP7787, a new protector against cisplatin-induced side-effects. Biochem Pharmacol. 2004 Aug 1;68(3):493-502. PubMed PMID: 15242815.

11: Jakupec MA, Galanski M, Keppler BK. The effect of cytoprotective agents in platinum anticancer therapy. Met Ions Biol Syst. 2004;42:179-208. Review. PubMed PMID: 15206103.

12: Goren MP, Epelman S, Bush DA. Urine mesna excretion after intravenous and oral dosing in ifosfamide-treated children. Cancer Chemother Pharmacol. 2004 Sep;54(3):237-40. Epub 2004 Jun 4. PubMed PMID: 15184993.

13: Verschraagen M, Boven E, Torun E, Erkelens CA, Hausheer FH, van der Vijgh WJ. Pharmacokinetic behaviour of the chemoprotectants BNP7787 and mesna after an i.v. bolus injection in rats. Br J Cancer. 2004 Apr 19;90(8):1654-9. PubMed PMID: 15083199; PubMed Central PMCID: PMC2410273.

14: Reilly RT. BNP-7787 (BioNumerik/Baxter Oncology/Grelan). IDrugs. 2004 Jan;7(1):64-9. Review. PubMed PMID: 14730469.

15: Mace JR, Keohan ML, Bernardy H, Junge K, Niebch G, Romeis P, Thoma A, Wagner T, Mueller U, Demetri G, Baker LH. Crossover randomized comparison of intravenous versus intravenous/oral mesna in soft tissue sarcoma treated with high-dose ifosfamide. Clin Cancer Res. 2003 Dec 1;9(16 Pt 1):5829-34. PubMed PMID: 14676103.

16: Verschraagen M, Boven E, Ruijter R, van der Born K, Berkhof J, Hausheer FH, van der Vijgh WJ. Pharmacokinetics and preliminary clinical data of the novel chemoprotectant BNP7787 and cisplatin and their metabolites. Clin Pharmacol Ther. 2003 Aug;74(2):157-69. PubMed PMID: 12891226.

17: Hausheer FH, Kochat H, Parker AR, Ding D, Yao S, Hamilton SE, Petluru PN, Leverett BD, Bain SH, Saxe JD. New approaches to drug discovery and development: a mechanism-based approach to pharmaceutical research and its application to BNP7787, a novel chemoprotective agent. Cancer Chemother Pharmacol. 2003 Jul;52 Suppl 1:S3-15. Epub 2003 Jun 18. Review. PubMed PMID: 12819940.

18: Verschraagen M, Boven E, Zegers I, Hausheer FH, Van der Vijgh WJ. Pharmacokinetics of BNP7787 and its metabolite mesna in plasma and ascites: a case report. Cancer Chemother Pharmacol. 2003 Jun;51(6):525-9. Epub 2003 May 15. PubMed PMID: 12750838.

19: Li YS, Wang Y, Church JS, Garzena F, Zhang Z, An D. Vibrational spectroscopic studies of mesna and dimesna. Spectrochim Acta A Mol Biomol Spectrosc. 2003 Jun;59(8):1791-8. PubMed PMID: 12736065.

20: Verschraagen M, Kedde MA, Hausheer FH, Van Der Vijgh WJ. The chemical reactivity of BNP7787 and its metabolite mesna with the cytostatic agent cisplatin: comparison with the nucleophiles thiosulfate, DDTC, glutathione and its disulfide GSSG. Cancer Chemother Pharmacol. 2003 Jun;51(6):499-504. Epub 2003 Apr 25. PubMed PMID: 12715205.

21: Verschraagen M, Zwiers TH, Torun E, Donker MG, Reinhoud NJ, Van der Vijgh WJ. Simultaneous determination of BNP7787 and its metabolite mesna in plasma and tissue by micro-HPLC with a dual electrochemical detector. J Pharm Sci. 2003 May;92(5):1040-50. PubMed PMID: 12712424.

22: Pendyala L, Schwartz G, Smith P, Zdanowicz J, Murphy M, Hausheer F. Modulation of plasma thiols and mixed disulfides by BNP7787 in patients receiving paclitaxel/cisplatin therapy. Cancer Chemother Pharmacol. 2003 May;51(5):376-84. Epub 2003 Apr 8. PubMed PMID: 12682786.

23: Boven E, Verschraagen M, Hulscher TM, Erkelens CA, Hausheer FH, Pinedo HM, van der Vijgh WJ. BNP7787, a novel protector against platinum-related toxicities, does not affect the efficacy of cisplatin or carboplatin in human tumour xenografts. Eur J Cancer. 2002 May;38(8):1148-56. PubMed PMID: 12008205.

24: Senior K. Supercomputer-designed drug protects against chemotherapy toxicity. Lancet Oncol. 2000 Dec;1:198. PubMed PMID: 11905631.

25: Verschraagen M, Zwiers TH, de Koning PE, Welink J, van der Vijgh WJ. Quantification of BNP7787 (dimesna) and its metabolite mesna in human plasma and urine by high-performance liquid chromatography with electrochemical detection. J Chromatogr B Biomed Sci Appl. 2001 Apr 5;753(2):293-302. PubMed PMID: 11334343.

26: Kelland LR. Meeting report on 8th International Symposium on Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy. J Inorg Biochem. 1999 Oct;77(1-2):121-4. PubMed PMID: 10626364.

27: Foxall PJ, Singer JM, Hartley JM, Neild GH, Lapsley M, Nicholson JK, Souhami RL. Urinary proton magnetic resonance studies of early ifosfamide-induced nephrotoxicity and encephalopathy. Clin Cancer Res. 1997 Sep;3(9):1507-18. PubMed PMID: 9815837.

28: Goren MP, Houle JM, Bush DA, Li JT, Newman CE, Brade WP. Similar bioavailability of single-dose oral and intravenous mesna in the blood and urine of healthy human subjects. Clin Cancer Res. 1998 Oct;4(10):2313-20. PubMed PMID: 9796960.

29: Hausheer FH, Kanter P, Cao S, Haridas K, Seetharamulu P, Reddy D, Petluru P, Zhao M, Murali D, Saxe JD, Yao S, Martinez N, Zukowski A, Rustum YM. Modulation of platinum-induced toxicities and therapeutic index: mechanistic insights and first- and second-generation protecting agents. Semin Oncol. 1998 Oct;25(5):584-99. Review. PubMed PMID: 9783598.

30: Goren MP, Hsu LC, Li JT. Reduction of dimesna to mesna by the isolated perfused rat liver. Cancer Res. 1998 Oct 1;58(19):4358-62. PubMed PMID: 9766664.

31: Goren MP, Anthony LB, Hande KR, Johnson DH, Brade WP, Frazier MW, Bush DA, Li JT. Pharmacokinetics of an intravenous-oral versus intravenous-mesna regimen in lung cancer patients receiving ifosfamide. J Clin Oncol. 1998 Feb;16(2):616-21. PubMed PMID: 9469350.

32: el-Yazigi A, Ezzat A. Pharmacokinetic monitoring of anticancer drugs at King Faisal Specialist Hospital, Riyadh, Saudi Arabia. Ther Drug Monit. 1997 Aug;19(4):390-3. PubMed PMID: 9263378.

33: el-Yazigi A, Ernst P, al-Rawithi S, Legayada E, Raines DA. Pharmacokinetics of mesna and dimesna after simultaneous intravenous bolus and infusion administration in patients undergoing bone marrow transplantation. J Clin Pharmacol. 1997 Jul;37(7):618-24. PubMed PMID: 9243355.

34: Kurowski V, Wagner T. Urinary excretion of ifosfamide, 4-hydroxyifosfamide, 3- and 2-dechloroethylifosfamide, mesna, and dimesna in patients on fractionated intravenous ifosfamide and concomitant mesna therapy. Cancer Chemother Pharmacol. 1997;39(5):431-9. PubMed PMID: 9054957.

35: Mohrmann M, Küpper N, Schönfield B, Brandis M. Ifosfamide and mesna: effects on the Na/H exchanger activity in renal epithelial cells in culture (LLC-PK1). Ren Physiol Biochem. 1995 May-Jun;18(3):118-27. PubMed PMID: 7542792.

36: el-Yazigi A, Yusuf A, al-Rawithi S. Liquid chromatographic analysis of mesna and dimesna in plasma and urine of patients treated with mesna. Ther Drug Monit. 1995 Apr;17(2):153-8. PubMed PMID: 7624904.

37: Mohrmann M, Ansorge S, Schönfeld B, Brandis M. Dithio-bis-mercaptoethanesulphonate (DIMESNA) does not prevent cellular damage by metabolites of ifosfamide and cyclophosphamide in LLC-PK1 cells. Pediatr Nephrol. 1994 Aug;8(4):458-65. PubMed PMID: 7524598.

38: Stofer-Vogel B, Cerny T, Borner M, Lauterburg BH. Oral bioavailability of mesna tablets. Cancer Chemother Pharmacol. 1993;32(1):78-81. PubMed PMID: 8462128.

39: Pea F, Mazzo M, Miglioli PA, Casiglia E, Pessina A, Moretti V. Serum concentrations of sodium 2-mercaptoethanesulfonate (MESNA) and its metabolite, disulfide form (DIMESNA), in volunteers after oral dosing: a comparison between MESNA and ARGIMESNA. Pharmacol Res. 1992 Feb-Mar;25 Suppl 1:85-6. PubMed PMID: 1508821.

40: Devasagayam TP, Sundquist AR, Di Mascio P, Kaiser S, Sies H. Activity of thiols as singlet molecular oxygen quenchers. J Photochem Photobiol B. 1991 Apr;9(1):105-16. PubMed PMID: 1907641.

41: Blomgren H, Hallström M, Hillgren H. Antitumor activity of 2-mercaptoethanesulfonate (mesna) in vitro. Its potential use in the treatment of superficial bladder cancer. Anticancer Res. 1991 Mar-Apr;11(2):773-6. PubMed PMID: 1905905.

42: Dorr RT. Chemoprotectants for cancer chemotherapy. Semin Oncol. 1991 Feb;18(1 Suppl 2):48-58. Review. PubMed PMID: 1899489.

43: Goren MP, Lyman BA, Li JT. The stability of mesna in beverages and syrup for oral administration. Cancer Chemother Pharmacol. 1991;28(4):298-301. PubMed PMID: 1908750.

44: Leeuwenkamp OR, Neijt JP, van der Vijgh WJ, Pinedo HM. Reaction kinetics of cisplatin and its monoaquated species with the modulating agents (di)mesna and thiosulphate. Eur J Cancer. 1991;27(10):1243-7. PubMed PMID: 1835593.

45: Blomgren H, Hallström M, Hillgren H. Antitumor activity of 2-mercaptoethanesulfonate (mesna) in vitro. Methods Find Exp Clin Pharmacol. 1990 Dec;12(10):691-7. PubMed PMID: 2129247.

46: Schoenike SE, Dana WJ. Ifosfamide and mesna. Clin Pharm. 1990 Mar;9(3):179-91. Review. PubMed PMID: 2107997.

47: Leeuwenkamp OR, van der Vijgh WJ, Neijt JP, Pinedo HM. Reaction kinetics of cisplatin and its monoaquated species with the (potential) renal protecting agents (di)mesna and thiosulfate. Estimation of the effect of protecting agents on the plasma and peritoneal AUCs of CDDP. Cancer Chemother Pharmacol. 1990;27(2):111-4. PubMed PMID: 2174306.

48: Petru E, Schmähl D. Anticancer drugs: second malignancies--risk reduction. Cancer Treat Rev. 1987 Dec;14(3-4):337-43. PubMed PMID: 3125969.

49: Bast A, Haenen GR, Savenije-Chapel EM. Inhibition of rat hepatic microsomal lipid peroxidation by mesna via glutathione. Arzneimittelforschung. 1987 Sep;37(9):1043-5. PubMed PMID: 3124863.

50: Shaw IC, Weeks MS. Excretion of disodium bis-2-mercaptoethanesulphonate (dimesna) in the urine of volunteers after oral dosing. Eur J Cancer Clin Oncol. 1987 Jul;23(7):933-5. PubMed PMID: 3117563.

51: Shaw IC, Graham MI. Mesna--a short review. Cancer Treat Rev. 1987 Jun;14(2):67-86. Review. PubMed PMID: 3119211.

52: James CA, Mant TG, Rogers HJ. Pharmacokinetics of intravenous and oral sodium 2-mercaptoethane sulphonate (mesna) in normal subjects. Br J Clin Pharmacol. 1987 May;23(5):561-8. PubMed PMID: 3109461; PubMed Central PMCID: PMC1386192.

53: James CA, Rogers HJ. Estimation of mesna and dimesna in plasma and urine by high-performance liquid chromatography with electrochemical detection. J Chromatogr. 1986 Oct 31;382:394-8. PubMed PMID: 3097045.

54: Shaw IC, Weeks MS. Interaction between mesna and selected transition metals in vitro and in vivo. Arzneimittelforschung. 1986 Jun;36(6):997-1000. PubMed PMID: 3091043.

55: Reuther H, Kohl M, Wildenauer DB. The interactions of mesna and dimesna with the sulfate exchange in human red blood cells. Arzneimittelforschung. 1986 Apr;36(4):763-5. PubMed PMID: 3087373.

56: Shaw IC, Graham MI, Jones MS. The fate of [14C]-mesna in the rat. Arzneimittelforschung. 1986 Mar;36(3):487-9. PubMed PMID: 3085684.

57: Al-Safi SA, Maddocks JL. Does 2-mercaptoethane sulphonate (mesna) prevent cyclophosphamide and azathioprine induced immunosuppression? In vitro studies. Br J Clin Pharmacol. 1986 Mar;21(3):267-70. PubMed PMID: 2938613; PubMed Central PMCID: PMC1400868.

58: Brock N, Pohl J. Prevention of urotoxic side effects by regional detoxification with increased selectivity of oxazaphosphorine cytostatics. IARC Sci Publ. 1986;(78):269-79. PubMed PMID: 3108156.

59: Habs M, Schmähl D. New experimental approaches to reducing carcinogenicity in animals by modifying regimens. IARC Sci Publ. 1986;(78):177-85. PubMed PMID: 3108155.

60: Ikeuchi I, Amano T. Simultaneous determination of 2-mercaptoethanesulfonate and its disulfide in human urine by isotachophoresis. Chem Pharm Bull (Tokyo). 1985 Jul;33(7):3016-9. PubMed PMID: 3936628.

61: Schmähl D, Habs M, Tacchi AM. [Prevention of tumor formation in the bladder by sodium-2-mercaptoethane sulfonate (mesna). Experimental studies and clinical consequences]. Urologe A. 1984 Sep;23(5):291-6. German. PubMed PMID: 6438859.

62: Brock N, Hilgard P, Pohl J, Ormstad K, Orrenius S. Pharmacokinetics and mechanism of action of detoxifying low-molecular-weight thiols. J Cancer Res Clin Oncol. 1984;108(1):87-97. PubMed PMID: 6746722.

63: Burkert H, Lücker PW, Wetzelsberger N, Breuel HP. Bioavailability of orally administered mesna. Arzneimittelforschung. 1984;34(11):1597-600. PubMed PMID: 6441581.

64: Schmähl D, Habs MR. Prevention of cyclophosphamide-induced carcinogenesis in the urinary bladder of rats by administration of mesna. Cancer Treat Rev. 1983 Sep;10 Suppl A:57-61. PubMed PMID: 6414697.

65: Habs MR, Schmähl D. 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):606-9. PubMed PMID: 6401591.

66: Ormstad K, Orrenius S, Låstbom T, Uehara N, Pohl J, Stekar J, Brock N. Pharmacokinetics and metabolism of sodium 2-mercaptoethanesulfonate in the rat. Cancer Res. 1983 Jan;43(1):333-8. PubMed PMID: 6401168.

67: Ormstad K, Uehara N. Renal transport and disposition of Na-2-mercaptoethane sulfonate disulfide (dimesna) in the rat. FEBS Lett. 1982 Dec 27;150(2):354-8. PubMed PMID: 6819161.

68: Brock N, Stekar J. [Prevention of urotoxic actions of cyclophosphamide and ifosfamide by dimesna (preliminary communication) (author's transl)]. Arzneimittelforschung. 1982;32(5):486-7. German. PubMed PMID: 6809014.

69: Hermans JM, Hutten TJ, van der Drift C, Vogels GD. Analysis of coenzyme m (2-mercaptoethanesulfonic acid) derivatives by isotachophoresis. Anal Biochem. 1980 Aug;106(2):363-6. PubMed PMID: 6778250.

70: Balch WE, Wolfe RS. New approach to the cultivation of methanogenic bacteria: 2-mercaptoethanesulfonic acid (HS-CoM)-dependent growth of Methanobacterium ruminantium in a pressureized atmosphere. Appl Environ Microbiol. 1976 Dec;32(6):781-91. PubMed PMID: 827241; PubMed Central PMCID: PMC170461.