BRL-15572 Dihydrochloride

Catalog No.S2677 Batch:S267701

Technical Data

Formula

C₂₅H₂₇ClN₂O.2HCl

Molecular Weight

479.87

CAS No.

193611-72-2

Solubility (25°C)*

In vitro

DMSO

96 mg/mL (200.05 mM)

Ethanol

40 mg/mL (83.35 mM)

Water

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution

30%propylene glycol 1 5%Tween80 2 65%D5W

20.0mg/ml

Taking the 1 mL working solution as an example, add 300 μL of clarified propylene glycol stock solution of 66.67 mg/ml to 50 μL of Tween 80, mix evenly to clarify it; then continue to add 650 μL of D5W to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

BRL-15572 is a 5-HT1D receptor antagonist with pK_i of 7.9, also shows a considerable affinity at 5-HT1A and 5-HT2B receptors, exhibiting 60-fold selectivity over 5-HT1B receptor.

Targets

5-HT1D ^[1]	5-HT1A ^[1]	5-HT2B ^[1]	5-HT2A ^[1]	5-HT7 ^[1]	View More
7.9(pKi)	7.7(pKi)	7.4(pKi)	6.6(pKi)	6.3(pKi)	View More

In vitro

BRL-15572 displays high affinity and selectivity for h5-HT_1D receptors. BRL-15572 has 60-fold higher affinity for h5-HT_1D than 5-HT_1B receptors. BRL-15572 binds to h5-HT_1B and h5-HT_1D receptors with pKB of less than 6 and 7.1, respectively. BRL-15572 stimulates [³⁵S]GTP γ S binding in both cell lines, with potencies that correlated with their receptor binding affinities in both h5-HT_1B and h5-HT_1D receptor expressing cell lines. BRL-15572 reveals receptor binding affinities for 5-HT_1A, 5-HT_1B, 5-HT_1E, 5-HT_1F, 5-HT_2A, 5-HT_2B, 5-HT_2C, 5-HT₆ and 5-HT₇ with pK_i of 7.7, 6.1, 5.2, 6.0, 6.6, 7.4, 6.2, 5.9 and 6.3, respectively. In the h5-HT_1D cell line, both BRL-15572 (1 µM) shifts the 5-HT concentration response curve with pK_B of 7.1, respectively. BRL-15572 does have moderately high affinity at human 5-HT_1A and 5-HT_2B receptors. ^[1] In human atrial appendages, the electrically evoked tritium overflow is inhibited by 5-HT in a manner susceptible to antagonism by BRL-15572 (300 nM; 23 times Ki at h5-HT1D receptors). ^[2] The inhibitory effect of 5-HT on the K⁺-evoked overflow of glutamate is antagonized by the h5-HT_1D receptor ligand BRL-15572. BRL-15572 (1 μM) is unable to modify the effect of 5-HT at the autoreceptor regulating [³H]5-HT release. ^[3] The selective 5-HT1D/1B receptor antagonist BRL 15572 inhibits the effect of the agonist L-694 247. ^[4]

In vivo

In diabetic pithed rats, administration of the selective 5-HT_1D receptor antagonist BRL-15572 (2 mg/kg) does not modify the decreased HR induced by vagal electrical stimulation. The effects of L-694,247 (50 μg/kg), a selective agonist for non-rodent 5-HT_1B and 5-HT_1D receptors, on the vagally induced bradycardia are not apparent after pretreatment with BRL-15572. ^[5]

Features

A selective 5-HT_1D/1B receptor antagonist.

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines CHO cells expressing the h5-HT_1B or h5-HT_1D receptors Concentrations 0 μM -10 μM Incubation Time 30 minutes Method [³⁵S]GTPγS binding studies. [³⁵S]GTPγS binding studies in CHO cells expressing the h5-HT_1B or h5-HT_1D receptors are performed. In brief, membranes from 1 × 10⁶ cells are preincubated at 30°C for 30 minutes, in HEPES buffer (HEPES [20 mM], MgCl₂ [3 mM], NaCl [100 mM], ascorbate [0.2 mM]), containing GDP (10 µ M), with or without BRL-15572. The reaction is started by the addition of 10 µL of [³⁵S]GTPγS (100 pM, assay concentration) followed by a further 30 minutes incubation at 30°C. Non-specific binding is determined by addition of unlabelled GTPγS (10 µM), prior to the addition of cells. The reaction is stopped by rapid filtration using Whatman GF/B grade filters followed by five washes with ice-cold HEPES buffer. Radioactivity is determined by liquid scintillation spectrometry.
Animal Study:^{^[5]}	Animal Models Male Wistar rats with diabetes Dosages 1 mg/kg, 2 mg/kg Administration Administered via i.v.

Cell Assay:^{^[1]}

Cell lines
CHO cells expressing the h5-HT_1B or h5-HT_1D receptors
Concentrations
0 μM -10 μM
Incubation Time
30 minutes
Method
[³⁵S]GTPγS binding studies. [³⁵S]GTPγS binding studies in CHO cells expressing the h5-HT_1B or h5-HT_1D receptors are performed. In brief, membranes from 1 × 10⁶ cells are preincubated at 30°C for 30 minutes, in HEPES buffer (HEPES [20 mM], MgCl₂ [3 mM], NaCl [100 mM], ascorbate [0.2 mM]), containing GDP (10 µ M), with or without BRL-15572. The reaction is started by the addition of 10 µL of [³⁵S]GTPγS (100 pM, assay concentration) followed by a further 30 minutes incubation at 30°C. Non-specific binding is determined by addition of unlabelled GTPγS (10 µM), prior to the addition of cells. The reaction is stopped by rapid filtration using Whatman GF/B grade filters followed by five washes with ice-cold HEPES buffer. Radioactivity is determined by liquid scintillation spectrometry.

Animal Study:^{^[5]}

Animal Models
Male Wistar rats with diabetes
Dosages
1 mg/kg, 2 mg/kg
Administration
Administered via i.v.

References

+ Expand

Selleck's BRL-15572 Dihydrochloride has been cited by 5 publications

VEGFR2 promotes central endothelial activation and the spread of pain in inflammatory arthritis [Beazley-Long N Brain Behav Immun, 2018, 74:49-67]	PubMed: 29548992
An In Vitro Model for Identifying Cardiac Side Effects of Anesthetics [Chang ACY Anesth Analg, 2018, 10.1213/ANE.0000000000003757]	PubMed: 30198930
Methamphetamine modulates the production of interleukin-6 and tumor necrosis factor-alpha via the cAMP/PKA/CREB signaling pathway in lipopolysaccharide-activated microglia [Wang B Int Immunopharmacol, 2018, 56:168-178]	PubMed: 29414647
The role of PDE3B phosphorylation in the inhibition of lipolysis by insulin [DiPilato LM Mol Cell Biol, 2015, 35(16):2752-60]	PubMed: 26031333
Rapamycin prevents strong phosphorylation of p53 on serine 46 and attenuates activation of the p53 pathway in A549 lung cancer cells exposed to actinomycin D [Krześniak M Mech Ageing Dev, 2014, 139:11-21]	PubMed: 24915467

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SHIPPING AND STORAGE
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