Bumetanide

NKCC cotransporter inhibitor CAS# 28395-03-1

Bumetanide

Catalog No. BCC1119----Order now to get a substantial discount!

Product Name & Size Price Stock
Bumetanide:5mg $49.00 In stock
Bumetanide:10mg $83.00 In stock
Bumetanide:25mg $196.00 In stock
Bumetanide:50mg $343.00 In stock
Related Products

Quality Control of Bumetanide

Number of papers citing our products

Chemical structure

Bumetanide

3D structure

Chemical Properties of Bumetanide

Cas No. 28395-03-1 SDF Download SDF
PubChem ID 2471 Appearance Powder
Formula C17H20N2O5S M.Wt 364.42
Type of Compound N/A Storage Desiccate at -20°C
Synonyms Ro 10-6338; PF 1593
Solubility DMSO : ≥ 100 mg/mL (274.41 mM)
H2O : < 0.1 mg/mL (insoluble)
*"≥" means soluble, but saturation unknown.
Chemical Name 3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acid
SMILES CCCCNC1=C(C(=CC(=C1)C(=O)O)S(=O)(=O)N)OC2=CC=CC=C2
Standard InChIKey MAEIEVLCKWDQJH-UHFFFAOYSA-N
Standard InChI InChI=1S/C17H20N2O5S/c1-2-3-9-19-14-10-12(17(20)21)11-15(25(18,22)23)16(14)24-13-7-5-4-6-8-13/h4-8,10-11,19H,2-3,9H2,1H3,(H,20,21)(H2,18,22,23)
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of Bumetanide

DescriptionBumetanide (Bumex) is a loop diuretic of the sulfamyl category to treat heart failure.

Bumetanide Dilution Calculator

Concentration (start)
x
Volume (start)
=
Concentration (final)
x
Volume (final)
 
 
 
C1
V1
C2
V2

calculate

Bumetanide Molarity Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
g/mol

calculate

Preparing Stock Solutions of Bumetanide

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 2.7441 mL 13.7204 mL 27.4409 mL 54.8817 mL 68.6022 mL
5 mM 0.5488 mL 2.7441 mL 5.4882 mL 10.9763 mL 13.7204 mL
10 mM 0.2744 mL 1.372 mL 2.7441 mL 5.4882 mL 6.8602 mL
50 mM 0.0549 mL 0.2744 mL 0.5488 mL 1.0976 mL 1.372 mL
100 mM 0.0274 mL 0.1372 mL 0.2744 mL 0.5488 mL 0.686 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

Organizitions Citing Our Products recently

 
 
 

Calcutta University

University of Minnesota

University of Maryland School of Medicine

University of Illinois at Chicago

The Ohio State University

University of Zurich

Harvard University

Colorado State University

Auburn University

Yale University

Worcester Polytechnic Institute

Washington State University

Stanford University

University of Leipzig

Universidade da Beira Interior

The Institute of Cancer Research

Heidelberg University

University of Amsterdam

University of Auckland
TsingHua University
TsingHua University
The University of Michigan
The University of Michigan
Miami University
Miami University
DRURY University
DRURY University
Jilin University
Jilin University
Fudan University
Fudan University
Wuhan University
Wuhan University
Sun Yat-sen University
Sun Yat-sen University
Universite de Paris
Universite de Paris
Deemed University
Deemed University
Auckland University
Auckland University
The University of Tokyo
The University of Tokyo
Korea University
Korea University

Background on Bumetanide

Loop diuretic that inhibits the Na+/2Cl-/K+ (NKCC) cotransporter. More potent than furosemide.

Featured Products
New Products
 

References on Bumetanide

Bumetanide increases Cl--dependent short-circuit current in late distal colon: Evidence for the presence of active electrogenic Cl- absorption.[Pubmed:28152000]

PLoS One. 2017 Feb 2;12(2):e0171045.

Mammalian colonic epithelia consist of cells that are capable of both absorbing and secreting Cl-. The present studies employing Ussing chamber technique identified two opposing short-circuit current (Isc) responses to basolateral Bumetanide in rat distal colon. Apart from the transepithelial Cl--secretory Isc in early distal colon that was inhibited by Bumetanide, Bumetanide also stimulated Isc in late distal colon that had not previously been identified. Since Bumetanide inhibits basolateral Na+-K+-2Cl- cotransporter (NKCC) in crypt cells and basolateral K+-Cl- cotransporter (KCC) in surface epithelium, we proposed this stimulatory Isc could represent a KCC-mediated Cl- absorptive current. In support of this hypothesis, ion substitution experiments established Cl- dependency of this absorptive Isc and transport inhibitor studies demonstrated the involvement of an apical Cl- conductance. Current distribution and RNA sequencing analyses revealed that this Cl- absorptive Isc is closely associated with epithelial Na+ channel (ENaC) but is not dependent on ENaC activity. Thus, inhibition of ENaC by 10 muM amiloride or benzamil neither altered the direction nor its activity. Physiological studies suggested that this Cl- absorptive Isc senses dietary Cl- content; thus when dietary Cl- was low, Cl- absorptive Isc was up-regulated. In contrast, when dietary Cl- was increased, Cl- absorptive Isc was down-regulated. We conclude that an active Cl- extrusion mechanism exists in ENaC-expressing late distal colon and likely operates in parallel with ENaC to facilitate NaCl absorption.

Bumetanide reduce the seizure susceptibility induced by pentylenetetrazol via inhibition of aberrant hippocampal neurogenesis in neonatal rats after hypoxia-ischemia.[Pubmed:28161194]

Brain Res Bull. 2017 Apr;130:188-199.

Hypoxia-ischemia brain damage (HIBD) is one of prevalent causes of neonatal mortality and morbidity. Our data demonstrated that hypoxia-ischemia (HI) induced Na(+)-K(+)-Cl(-)-co-transporter 1 (NKCC1) increasing in hippocampus. Previous studies demonstrated that NKCC1 regulates various stages of neurogenesis. In this study, we studied the role of increased NKCC1 in regulating of HI-induced neurogenesis. HIBD model was established in 7days old Sprague-Dawley rat pup, and the expression of NKCC1 was detected by western blot and qPCR. Brain electrical activity in freely rats was monitored by electroencephalography (EEG) recordings. HI-induced neurogenesis was detected by immunofluorescence staining. Neurobehavioral test was to investigate the neuro-protective role of Bumetanide, an inhibitor of NKCC1, on neonatal rats after HI. The results showed that Bumetanide treatment significantly reduced brain electrical activity and the seizure stage of epilepsy induced by pentylenetetrazol (PTZ) in vivo after HI. In addition, Bumetanide restored aberrant hippocampal neurogenesis and associated cognitive function. Our data demonstrated that Bumetanide reduces the susceptibility of epilepsy induced by PTZ in rats suffering from HI injury during neonatal period via restoring the ectopic newborn neurons in dentate gyrus (DG) and cognitive function.

Effects of bumetanide on neurobehavioral function in children and adolescents with autism spectrum disorders.[Pubmed:28291262]

Transl Psychiatry. 2017 Mar 14;7(3):e1056.

In animal models of autism spectrum disorder (ASD), the NKCC1 chloride-importer inhibitor Bumetanide restores physiological (Cl(-))i levels, enhances GABAergic inhibition and attenuates electrical and behavioral symptoms of ASD. In an earlier phase 2 trial; Bumetanide reduced the severity of ASD in children and adolescents (3-11 years old). Here we report the results of a multicenter phase 2B study primarily to assess dose/response and safety effects of Bumetanide. Efficacy outcome measures included the Childhood Autism Rating Scale (CARS), the Social Responsive Scale (SRS) and the Clinical Global Impressions (CGI) Improvement scale (CGI-I). Eighty-eight patients with ASD spanning across the entire pediatric population (2-18 years old) were subdivided in four age groups and randomized to receive Bumetanide (0.5, 1.0 or 2.0 mg twice daily) or placebo for 3 months. The mean CARS value was significantly improved in the completers group (P: 0.015). Also, 23 treated children had more than a six-point improvement in the CARS compared with only one placebo-treated individual. Bumetanide significantly improved CGI (P: 0.0043) and the SRS score by more than 10 points (P: 0.02). The most frequent adverse events were hypokalemia, increased urine elimination, loss of appetite, dehydration and asthenia. Hypokalemia occurred mainly at the beginning of the treatment at 1.0 and 2.0 mg twice-daily doses and improved gradually with oral potassium supplements. The frequency and incidence of adverse event were directly correlated with the dose of Bumetanide. Therefore, Bumetanide improves the core symptoms of ASD and presents a favorable benefit/risk ratio particularly at 1.0 mg twice daily.

Multiple blood-brain barrier transport mechanisms limit bumetanide accumulation, and therapeutic potential, in the mammalian brain.[Pubmed:28192112]

Neuropharmacology. 2017 May 1;117:182-194.

There is accumulating evidence that Bumetanide, which has been used over decades as a potent loop diuretic, also exerts effects on brain disorders, including autism, neonatal seizures, and epilepsy, which are not related to its effects on the kidney but rather mediated by inhibition of the neuronal Na-K-Cl cotransporter isoform NKCC1. However, following systemic administration, brain levels of Bumetanide are typically below those needed to inhibit NKCC1, which critically limits its clinical use for treating brain disorders. Recently, active efflux transport at the blood-brain barrier (BBB) has been suggested as a process involved in the low brain:plasma ratio of Bumetanide, but it is presently not clear which transporters are involved. Understanding the processes explaining the poor brain penetration of Bumetanide is needed for developing strategies to improve the brain delivery of this drug. In the present study, we administered probenecid and more selective inhibitors of active transport carriers at the BBB directly into the brain of mice to minimize the contribution of peripheral effects on the brain penetration of Bumetanide. Furthermore, in vitro experiments with mouse organic anion transporter 3 (Oat3)-overexpressing Chinese hamster ovary cells were performed to study the interaction of Bumetanide, Bumetanide derivatives, and several known inhibitors of Oats on Oat3-mediated transport. The in vivo experiments demonstrated that the uptake and efflux of Bumetanide at the BBB is much more complex than previously thought. It seems that both restricted passive diffusion and active efflux transport, mediated by Oat3 but also organic anion-transporting polypeptide (Oatp) Oatp1a4 and multidrug resistance protein 4 explain the extremely low brain concentrations that are achieved after systemic administration of Bumetanide, limiting the use of this drug for targeting abnormal expression of neuronal NKCC1 in brain diseases.

Ion and bumetanide binding by the Na-K-Cl cotransporter. Importance of transmembrane domains.[Pubmed:9305921]

J Biol Chem. 1997 Sep 26;272(39):24556-62.

The Na-K-Cl cotransporter (NKCC) plays a key role in electrolyte secretion and absorption across polarized epithelia. The structure of the Na-K-Cl cotransporter transport protein is not known, but from analysis of the primary amino acid sequence and biochemical studies, it has been inferred that the protein has large cytoplasmic N and C termini and a hydrophobic central domain containing 12 transmembrane helices. Both the central domain and the C-terminal domain are highly conserved within the cation-chloride cotransporter family. This paper examines the role of these three domains in interacting with the transported ions and with the inhibitor Bumetanide. We have used a chimera approach, exploiting the functional differences between the structurally similar shark and human secretory Na-K-Cl cotransporters (sNKCC1 and hNKCC1). These transporters are 74% identical to one another and have similar transport and regulatory behaviors; however, sNKCC1 differs markedly from hNKCC1 with regard to apparent affinities for the cotransported ions and for Bumetanide. We prepared six sNKCC1-hNKCC1 chimeras in which N and C termini were interchanged between species. When transfected in HEK-293 cells, each chimera carried out Bumetanide-sensitive 86Rb influx, demonstrating transporter synthesis and cell surface delivery. Monoclonal antibodies J3 and J7 were used to detect the chimeric proteins, and the epitopes for these antibodies were localized to residues 49-196 and 1050-1168, respectively, in the shark sequence. For each of two chimeras that were examined, the time course of activation in low Cl- medium was the same as for the parent proteins; activation was found to proceed through a change in Vmax rather than Km. For the six chimeras, the apparent affinities for Na+, K+, Cl-, and Bumetanide segregated exactly according to whether the large hydrophobic central domain was derived from sNKCC1 or hNKCC1. Significantly, the well-conserved C terminus does not appear to contain residues involved in the shark-human affinity differences. These results demonstrate that residues involved with ion translocation and inhibitor binding are within the large central domain that contains the 12 predicted transmembrane helices.

Characteristics and functions of Na-K-Cl cotransport in epithelial tissues.[Pubmed:3303961]

Am J Physiol. 1987 Aug;253(2 Pt 1):C177-92.

This review summarizes our present understanding of Na-K-Cl cotransport and its physiological role in absorption and secretion of electrolytes and water in epithelial tissues. In the past several years an extensive literature about this cotransporter has developed due to its widespread distribution in a variety of cell types and its essential role in fluid and electrolyte transport in several epithelial tissues. We summarize this literature and speculate on the future characterization of this transport system. Although this review focuses on cotransport as it relates to absorptive and secretory processes in epithelia, important information concerning the pharmacology, stoichiometry, and regulation of Na-K-Cl cotransport in nonepithelial systems (i.e., erythrocytes, fibroblasts, squid axon, etc.) has been included to supplement areas that are less well established in the epithelial literature.

Description

Bumetanide (Ro 10-6338;PF 1593) is a selective Na+-K+-Cl- cotransporter 1 (NKCC1) inhibitor, weakly inhibits NKCC2, with IC50s of 0.68 and 4.0 μM for hNKCC1A and hNKCC2A, respectively.

Keywords:

Bumetanide,28395-03-1,Ro 10-6338; PF 1593,Natural Products,NKCC, buy Bumetanide , Bumetanide supplier , purchase Bumetanide , Bumetanide cost , Bumetanide manufacturer , order Bumetanide , high purity Bumetanide

Online Inquiry for:

      Fill out the information below

      • Size:Qty: - +

      * Required Fields

                                      Result: