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  4. Dimesna free acid

Dimesna (BNP-7787) free acid, the disulfide form of Mesna (HY-13679), is a platinum-related toxicity protective agent. Dimesna free acid converts to Mesna, which in turn inactivates toxic platinum substances. Dimesna free acid does not interfere with the antitumor activity of platinum compounds. Dimesna free acid does not affect the antiproliferative effects of Cisplatin (HY-17394) or Carboplatin (HY-17393). Dimesna free acid counteracts Cisplatin-induced nephrotoxicity. Dimesna free acid exerts selective protective effects on the kidneys. Dimesna free acid can be used in studies related to ovarian cancer and Cisplatin-induced nephrotoxicity.

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Dimesna free acid

Dimesna free acid Chemical Structure

CAS No. : 45127-11-5

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Description

Dimesna (BNP-7787) free acid, the disulfide form of Mesna (HY-13679), is a platinum-related toxicity protective agent. Dimesna free acid converts to Mesna, which in turn inactivates toxic platinum substances. Dimesna free acid does not interfere with the antitumor activity of platinum compounds. Dimesna free acid does not affect the antiproliferative effects of Cisplatin (HY-17394) or Carboplatin (HY-17393). Dimesna free acid counteracts Cisplatin-induced nephrotoxicity. Dimesna free acid exerts selective protective effects on the kidneys. Dimesna free acid can be used in studies related to ovarian cancer and Cisplatin-induced nephrotoxicity[2][3].

In Vitro

Dimesna (0-5.0 mmol/L; 1-24 h) free acid alone exerts no effect on total protein, thymidine incorporation or uridine incorporation in LLC-PK1 cells, and fails to protect LLC-PK1 cells from toxicity induced by ifosfamide, cyclophosphamide, 4-hydroperoxyifosfamide, chloroacetaldehyde or acrolein[1].
Dimesna (≥2.0×103 μM; 96 h) free acid does not reduce the antiproliferative effects of cisplatin or carboplatin on A2780 or OVCAR-3 ovarian cancer cells, and only inhibits the growth of these cells when exposed for 96 h at a concentration of ≥2.0×103 μM[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Dimesna free acid Related Antibodies

Cell Viability Assay[1]

Cell Line: LLC-PK1 renal tubular cells
Concentration: 0-5.0 mmol/l (alone; co-incubated with ifosfamide/cyclophosphamide/4-OOH-ifosfamide/chloracetaldehyde/acrolein); 1.0-5.0 mmol/l (co-incubated with 4-OOH-cyclophosphamide)
Incubation Time: 1-24 h (alone); 1 h pre-incubation + 23 h co-incubation (with cytostatic metabolites)
Result: Had no significant effect on total protein, thymidine incorporation, or uridine incorporation at all tested concentrations and times when used alone.
Moderately stimulated thymidine incorporation, but had no significant effect on total protein or uridine incorporation when co-incubated with 150 μmol/l ifosfamide.
Had no significant effect on total protein, thymidine incorporation, or uridine incorporation when co-incubated with 150 μmol/l cyclophosphamide.
Further reduced total protein and thymidine incorporation at 1.0, 3.0, 5.0 mmol/l, and further reduced uridine incorporation at 3.0, 5.0 mmol/l (P < 0.05) when co-incubated with 75 μmol/l 4-OOH-cyclophosphamide.
Failed to protect cells from toxicity induced by 150 μmol/l 4-OOH-ifosfamide, with total protein, thymidine incorporation, and uridine incorporation remaining strongly reduced.
Failed to protect cells from toxicity induced by 75 μmol/l chloracetaldehyde, with no statistically significant difference in total protein, thymidine incorporation, or uridine incorporation compared to chloracetaldehyde alone.
Failed to protect cells from toxicity induced by 100 μmol/l acrolein, with total protein, thymidine incorporation, and uridine incorporation remaining severely reduced.
In Vivo

Dimesna (BNP-7787) (1000 mg/kg; i.v.) free acid does not interfere with the antitumour activity of cisplatin or carboplatin in OVCAR-3 ovarian cancer xenografts, and co-administration with 60 mg/kg carboplatin results in significantly greater tumour growth inhibition than carboplatin alone (specific growth delay of 4.72 vs. 4.01 for carboplatin alone)[2].
Dimesna (BNP-7787) (1000 mg/kg; i.v.; bolus injection) free acid administered to tumour-bearing Fischer rats results in preferential accumulation of its metabolite mesna in the kidney, with kidney mesna AUC0-t 4.5-fold higher than plasma mesna AUC0-t, while maintaining low mesna levels in plasma and tumour tissue relative to mesna administration[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Hsd: athymic nude-nu (female, 8-10 weeks old)[2]
Dosage: 1000 mg/kg (pre-cisplatin 5 mg/kg); 1000 mg/kg (pre-cisplatin 8 mg/kg); 1000 mg/kg (with carboplatin 60 mg/kg); 1000 mg/kg (with carboplatin 90 mg/kg); 1000 mg/kg (monotherapy)
Administration: i.v.; weekly ×2 (pre-cisplatin 5 mg/kg); i.v.; every 2 weeks ×2 (pre-cisplatin 8 mg/kg); i.v.; twice per treatment cycle, weekly ×2 (with carboplatin 60 mg/kg); i.v.; twice per treatment cycle, weekly ×2 (with carboplatin 90 mg/kg); i.v.; weekly ×2 (monotherapy)
Result: Exhibited mean maximum weight loss of 6.6±6.1%, no toxic deaths, specific growth delay of 3.48, and mean relative tumour volume of 2.55±0.42 on day 31 when given 5 minutes before 5 mg/kg cisplatin, with no significant difference in tumour growth inhibition compared to cisplatin alone.
Exhibited mean maximum weight loss of 24.8±9.2%, no toxic deaths, specific growth delay of 6.34, and mean relative tumour volume of 0.39±0.08 on day 31 when given 5 minutes before 8 mg/kg cisplatin, with no significant difference in tumour growth inhibition compared to amifostine-pretreated cisplatin.
Exhibited mean maximum weight loss of 9.9±11.9%, no toxic deaths, specific growth delay of 4.72, and mean relative tumour volume of 0.50±0.14 on day 31 when given with 60 mg/kg carboplatin, which was significantly smaller than carboplatin alone (P<0.01).
Exhibited mean maximum weight loss of 11.4±3.1%, 2 out of 6 mice died from toxicity, specific growth delay of 8.44, and mean relative tumour volume of 0.17±0.03 on day 31 when given with 90 mg/kg carboplatin.
Exhibited mean maximum weight loss of 0.0±3.2%, no toxic deaths, specific growth delay of 0.22, and mean relative tumour volume of 29.28±4.38 on day 31 as monotherapy, with no tumour growth inhibition observed.
Molecular Weight

282.38

Formula

C4H10O6S4
CAS No.
SMILES

O=S(O)(CCSSCCS(=O)(O)=O)=O
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Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
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Dimesna free acid Related Classifications

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    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

Dimesna45127-11-5BNP-7787BNP7787BNP 7787Drug DerivativeDrug derivativeInhibitorinhibitorinhibit

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