1. GPCR/G Protein
    Neuronal Signaling
  2. mAChR

Umeclidinium bromide (Synonyms: GSK573719A)

Cat. No.: HY-12100 Purity: 99.72%
Handling Instructions

Umeclidinium bromide is a novel mAChR antagonist. The affinity (Ki) of Umeclidinium bromide for the cloned human M1-M5 mAChRs ranges from 0.05 to 0.16 nM.

For research use only. We do not sell to patients.

Umeclidinium bromide Chemical Structure

Umeclidinium bromide Chemical Structure

CAS No. : 869113-09-7

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 295 In-stock
Estimated Time of Arrival: December 31
5 mg USD 264 In-stock
Estimated Time of Arrival: December 31
10 mg USD 420 In-stock
Estimated Time of Arrival: December 31
50 mg USD 840 In-stock
Estimated Time of Arrival: December 31
100 mg USD 1320 In-stock
Estimated Time of Arrival: December 31
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Top Publications Citing Use of Products
  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

Umeclidinium bromide is a novel mAChR antagonist. The affinity (Ki) of Umeclidinium bromide for the cloned human M1-M5 mAChRs ranges from 0.05 to 0.16 nM.

IC50 & Target

Ki: 0.16 nM (M1 mAChR), 0.15 nM (M2 mAChR), 0.06 nM (M3 mAChR), 0.05 nM (M4 mAChR), 0.13 nM (M4 mAChR)[1]

In Vitro

In human embryonic kidney 293 cells, Umeclidinium bromide (GSK573719A) inhibits the human ether-a-go-go-related gene channel tail current in a concentration-dependent manner (IC50=9.4 μM)[1]. Umeclidinium bromide, previously known as GSK573719, is a novel high-affinity specific mAChR antagonist. It is a potent agent that demonstrates slow functional reversibility at cloned human M3 mAChRs and at endogenous mAChR in isolated human bronchus[2].

In Vivo

When Umeclidinium bromide (GSK573719A) is given once daily to mice for 5 consecutive days (0.025 μg intranasally), the level of inhibition on the fifth day is modestly increased above that obtained after a single administration to the same mice (60 versus 35%, respectively). After the fifth day of dosing, the mice are rested for 5 additional days, allowing bronchomotor tone to return to baseline levels. On the sixth day, the mice receive one last dose of antagonist and are once again challenged with Mch. The level of inhibition is essentially the same as that found on the first day of testing, indicating that tolerance is not evident with repeated intranasal delivery of Umeclidinium bromide. By contrast, when Umeclidinium bromide is given orally (2.0 mg/kg) to mice at a dose 100 times the ED50 value (intranasal), there is no observable protection against an Mch challenge[1].

Clinical Trial
Solvent & Solubility
In Vitro: 

DMSO : ≥ 34 mg/mL (66.86 mM)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.9666 mL 9.8330 mL 19.6661 mL
5 mM 0.3933 mL 1.9666 mL 3.9332 mL
10 mM 0.1967 mL 0.9833 mL 1.9666 mL
*Please refer to the solubility information to select the appropriate solvent.
In Vivo:
  • 1.

    Umeclidinium is dissolved in DMSO and then in distilled water[3].

References
Kinase Assay
[1]

Ligand binding assays with Umeclidinium bromide (GSK573719A) and [3H]-N-methyl scopolamine (0.5 nM) are performed using a scintillation proximity assay for M1, M2, and M3 mAChRs and a filtration assay for M4 and M5 mAChRs. For the scintillation proximity assay assay, membranes are incubated with wheat germ agglutinin beads in 50 mM HEPES buffer, pH 7.4, at 4°C for 30 minutes and then with the radioligand in a 96-well OptiPlate for 2 hours at room temperature in the presence of vehicle (1% DMSO) or GSK573719 (0.01-300 nM). At the end of the incubation, the plates are centrifuged (for 5 minutes at 2000g), and radioactivity is counted. For the filtration assay, membranes (M4 and M5) are similarly incubated in HEPES buffer containing the radioligand for 2 hours at room temperature in the presence of vehicle (1% DMSO) or Umeclidinium bromide (0.03-300 nM). Atropine is used as a reference agent. Reactions are terminated by rapid filtration through GF/C filters (glass microfiber binder free 1.2 μ). Membranes are washed with ice-cold 50 mM HEPES and transferred to scintillation vials. Radioactivity is counted in a Scintillation Counter. Reactions are terminated by rapid filtration. Data are obtained from three independent experiments. Specific binding is determined by subtracting nonspecific binding (using 0.3 μM atropine) from total binding. The inhibition constant (Ki) for Umeclidinium bromide is calculated. Membranes containing M3 mAChRs are also incubated for 2 hours at room temperature with increasing concentrations of [3H]-N-methyl scopolamine (0.08-9.24 nM) in the presence or absence of Umeclidinium bromide (0.2-0.5 nM) in 50 mM HEPES, pH 7.4. Nonspecific binding is determined using 10 μM atropine. The saturation data are converted to a scatchard plot for analysis[1].

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

Animal Administration
[1]

Mice[1]
Age-matched male BALB/c mice (23-25 gm) are pretreated intranasally (50 μL per mouse) with vehicle (0.9% saline) or Umeclidinium bromide at intervals (0.25-48 hours) prior to methacholine challenge, and placed into individual plethysmograph chambers. Fresh air is supplied by bias flow pumps to the chambers. After baseline respiratory [enhanced pause (Penh)] values are collected, the mice received methacholine (30 mg/mL or EC80) by aerosol delivery (flow=1.6 mL/min×2 minutes). An average Penh is then calculated for 5 minutes. Penh=[(expiratory time/relaxation time)−1]×(peak expiratory flow/peak inspiratory flow), and relaxation time is the amount of time required for 70% of the tidal volume to expire. In some cases, animals are treated on multiple, consecutive days as described in the figure legends. The data are expressed as the mean±S.E.M. percent inhibition of Penh or (mean Penh value of vehicle treated group-Penh for each drug-treated animal) divided by (mean Penh value of vehicle treated group)×100%. Data are analyzed using commercially available software.

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

References
Molecular Weight

508.49

Formula

C₂₉H₃₄BrNO₂

CAS No.

869113-09-7

SMILES

OC(C12CC[N+](CC2)(CCOCC3=CC=CC=C3)CC1)(C4=CC=CC=C4)C5=CC=CC=C5.[Br-]

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Purity: 99.72%

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Product Name:
Umeclidinium bromide
Cat. No.:
HY-12100
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Umeclidinium bromide

Cat. No.: HY-12100