Analysis of BNP7787 thiol-disulfide exchange reactions in phosphate buffer and human plasma using microscale electrochemical high performance liquid chromatography

Shanmugarajah, Dakshine; Ding, Desheng; Huang, Quili; Chen, Xinghai; Kochat, Harry; Petluru, Pavankumar N.; Ayala, Philippe Y.; Parker, Aulma R.; Hausheer, Frederick H.

doi:10.1016/j.jchromb.2009.02.056

Cited by 15 publications

(16 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although BNP7787 is expected to remain predominantly in the disulfide form in the plasma (11,48), the intracellular environment and the interstitial space are likely venues for BNP7787 metabolism to a key metabolite, mesna (Fig. 6A), and we have reported in detail on thiol-disulfide exchange reactions that occur between BNP7787 and physiologic thiols previously (11,37,48).…”

Section: Discussionmentioning

confidence: 90%

“…In the absence of a protecting agent such as BNP7787-derived mesna, monoaquocisplatin is highly reactive and interacts most probably with surface-accessible Figure 6. A, BNP7787 thiol disulfide exchange reactions may occur intracellularly and/or in the interstitial space (11,37,48). B, proposed BNP7787-mediated oxidation of cysteine residues on the αβ-tubulin heterodimer.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

BNP7787-Mediated Modulation of Paclitaxel- and Cisplatin-Induced Aberrant Microtubule Protein Polymerization In vitro

Parker

Petluru

et al. 2010

Molecular Cancer Therapeutics

Self Cite

View full text Add to dashboard Cite

Taxane and platinum drugs are important agents in the treatment of cancer and have shown activity against a variety of tumors, including ovarian, breast, and lung cancer, either as single agents or in combination with other chemotherapy drugs. However, a serious and prevalent side effect of taxane (docetaxel and all formulations/derivatives of paclitaxel) and platinum (cisplatin, carboplatin, and oxaliplatin) agents is dose-limiting chemotherapy-induced peripheral neuropathy (CIPN). CIPN can result in treatment delays, dose modifications, and, in severe cases, discontinuation of chemotherapy. Consequently, effective treatments for CIPN are needed. Dimesna (BNP7787; Tavocept TM ; disodium 2,2′-dithio-bis-ethanesulfonate) is an investigational drug that is undergoing international clinical development as a treatment that is coadministered with first-line taxane and platinum combination chemotherapy in patients with inoperable advanced primary adenocarcinoma of the lung. BNP7787 is currently being developed with the objective of increasing the survival of cancer patients receiving taxane-and/or cisplatin-based chemotherapy. Additional data indicate that BNP7787 may also protect against common and serious chemotherapy-induced toxicities, including chemotherapy-induced anemia, nausea, emesis, nephrotoxicity, and neuropathy, without interfering with antitumor activity of the chemotherapeutic agent(s). Studies herein show that BNP7787 prevents aberrant microtubule protein (MTP) polymerization that is caused by exposure of MTP to paclitaxel or cisplatin. BNP7787 modulates paclitaxel-induced hyperpolymerization of MTP in a dose-dependent manner, and mesna, an in vivo metabolite of BNP7787, protects against time-dependent cisplatin-induced inactivation of MTP. We propose that interactions between BNP7787 and MTP may play a role in BNP7787-mediated protection against CIPN.Mol Cancer Ther; 9(9); 2558-67. ©2010 AACR.

show abstract

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

BNP7787-Mediated Modulation of Paclitaxel- and Cisplatin-Induced Aberrant Microtubule Protein Polymerization In vitro

Parker

Petluru

et al. 2010

Molecular Cancer Therapeutics

Self Cite

View full text Add to dashboard Cite

show abstract

“…Other techniques include High Performance Liquid Chromatography (HPLC) [9,10], capillary electrophoresis (CE) [10] and Raman spectroscopy [11]. In biological fluids, most of the methods published for MSN quantitation were HPLC methods [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Spectrofluorimetric Estimation of Some Sulfhydryl–Containing Drugs by Demasking Reaction of the Palladium Chelate of 8-Hydroxyquinoline-5-Sulfonic Acid

Rs¹,

Sf²,

Hewala³

et al. 2017

Pharm Anal Acta

View full text Add to dashboard Cite

A simple and sensitive spectrofluorimetric method has been developed for the determination of some selected sulfhydryl-containing drugs namely Acetylcysteine (ACS), Captopril (CAP) and Mesna (MSN).The method is based on the interaction of the drugs with potassium (5-sulfoxino) palladium II in alkaline medium in presence of magnesium ions, where the sulfhydryl group combines with palladium from the non-fluorescent potassium bis (5-sulfoxino) palladium II. The resulting 8-hydroxy-5-quinoline sulfonic acid coordinates with magnesium to form the fluorescent chelate that is a measure of the amount of sulfhydrl containing drug analyzed. The fluorescence intensity was measured at an emission wavelength of 485 nm, by excitation at 345 nm. All the experimental parameters affecting the reaction were studied and optimized. The proposed method was applicable over the concentration range of 0.04-0.44 µg/mL for the three drugs and was applied for their determination in bulk form and in pharmaceutical preparations without interference from common excipients. The assay results were statistically compared with those obtained from previously reported methods where no significant difference was found between them. The selectivity and the stability-indicating aspect of the proposed method were confirmed by preparing the disulphides of the studied drugs and applying the reaction to the parent drugs in presence of their disulphides where no interference was detected from these related substances. By virtue of its high sensitivity, the proposed method was also extended to analyze the drugs in spiked human plasma and urine.

show abstract

“…1,3,7 Many of the small molecule protective agents have limited utility in the clinic for treating cisplatin-induced nephrotoxicity due to adverse side effects, attenuation of antitumor activity, and/or disruption of the physiological thiol-disulfide ratios in plasma and intracellularly. 8,9 Accordingly, saline hydration and/or forced diuresis remains the standard of care in the clinic. 2,3 BNP7787 (disodium 2,2 -dithio-bis ethane sulfonate; Tavocept TM (BioNumerik Pharmaceuticals, Inc., San Antonio, TX, USA); Fig.…”

Section: Introductionmentioning

confidence: 99%

“…1) is a watersoluble investigational agent that is undergoing clinical development. [8][9][10][11][12][13] In rats, BNP7787 (intravenous) Figure 1. When cisplatin is administered, it enters the kidney cells by transporter-mediated or via free diffusion mechanisms and accumulates specifically in S3 segment of proximal tubule.…”

Section: Introductionmentioning

confidence: 99%

Accumulation of BNP7787 in Human Renal Proximal Tubule Cells

Hausheer

Ding

Shanmugarajah

et al. 2011

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

Analysis of BNP7787 thiol-disulfide exchange reactions in phosphate buffer and human plasma using microscale electrochemical high performance liquid chromatography

Cited by 15 publications

References 36 publications

BNP7787-Mediated Modulation of Paclitaxel- and Cisplatin-Induced Aberrant Microtubule Protein Polymerization In vitro

BNP7787-Mediated Modulation of Paclitaxel- and Cisplatin-Induced Aberrant Microtubule Protein Polymerization In vitro

Spectrofluorimetric Estimation of Some Sulfhydryl–Containing Drugs by Demasking Reaction of the Palladium Chelate of 8-Hydroxyquinoline-5-Sulfonic Acid

Accumulation of BNP7787 in Human Renal Proximal Tubule Cells

Contact Info

Product

Resources

About