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Purity: ≥98%
ICI-118551 HCl, the hydrochloride salt of ICI118551, is a novel, potent and highly selective β2 adrenergic receptor antagonist, with Kis of 0.7, 49.5 and 611 nM for β2, β1 and β3 receptors, respectively. Particularly in the pulmonary circulation, beta(2)-adrenoceptors play a significant role in regulating vascular tone. The beta(2)AR is directed by ICI 118551 binding to a G(i)-coupled form rather than a G(s)-coupled form (ligand-directed trafficking). ICI 118,551 directly causes a negative inotropic effect by acting as an agonist at the G(i)-coupled beta(2)AR. The negative inotropic effect is more likely to manifest in situations where beta(2)ARs are present and G(i) is elevated (failing human heart, TGbeta(2) mouse heart).
| Targets |
β2-adrenergic receptor ( Ki = 0.7 nM ); β1-adrenergic receptor ( Ki = 49.5 nM ); β3-adrenoceptor ( Ki = 611 nM )
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| ln Vitro |
ICI-118551 blocks cAMP accumulation by 50% (IC50 = 1.7 mM)[1]. Pharmacological experiments demonstrate that ICI 118551's right shift of the norepinephrine dose-response curve is mediated via a beta(2)-adrenoceptor/G(i/o) protein-dependent pathway, which enhances NO production in the endothelium. These findings are supported by the fact that ICI 118551 has no effect on beta-adrenoceptor and endothelial NO synthase knockout mice. In the isolated perfused lung model, ICI 118551 lowers pulmonary arterial pressure both in hypoxic and normoxic conditions while increasing vascular lumen diameter in lung sections[2]. While transgenic mice with elevated G(i) levels and a high beta(2)AR number exhibit normal basal contractility, they also exhibit a similar negative inotropic response to ICI 118,551. The negative inotropic effect of ICI 118,551 is amplified by employing an adenovirus to overexpress human beta(2)AR in rabbit myocytes. Following treatment of cells with pertussis toxin to inactivate G(i), the negative inotropic effects are blocked in human, rabbit, and mouse myocytes. In normal rat myocytes, overexpression of G(i)alpha(2) induces the effect de novo[5].
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| ln Vivo |
The beta 1-receptor mediated shortening of electromechanical systole (QS2I), rise in systolic pressure, and rise in renin are unaffected by ICI 118,551 after one week of treatment; however, these responses are inhibited by a dose factor of eight following propranolol. The beta 2-receptor-mediated rise in noradrenaline and fall in diastolic pressure are equally blocked by ICI 118,551 and propranolol. Blood pressure is lowered when ICI 118,551 selectively blocks beta 2[4].
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| Enzyme Assay |
The growth media are taken out of the wells and replaced with 50 uL of Hanks' balanced salt solution an hour before the assay. This solution also included 0.5 mM of MgCl2•6H2O, 0.4 mM of MgSO4•7H2O, 20 mM of N-2-hydroxyethylpiperazine-N'-2ethanesulfonic acid (HEPES), 1.2 mM of 3-isobutyl-1-methylxanthine (IBMX), 0.95 mM of CaCl2, and 0.05% of BSA. For dose-response studies, every plate is submerged in a shaking water bath at 37°C. In one study, five wells/dose/plate are added, and then 10 minutes are spent incubating different doses of isoproterenol (10-9-10-5 M) and β1- and β2-receptor-selective partial agonists (tazolol, prenalterol, salbutamol, and terbutaline, 10-6 and 10-5 M, respectively). Another study uses 10 μM isoproterenol to stimulate the cells, either with or without different doses of β-adrenoceptor antagonists. After 10 minutes, the incubations are stopped by adding 100 μL of 10% trichloroacetic acid (TCA), which results in a final TCA concentration of 5%. Samples are dehydrated at 80°C for an entire night before being resuspended in 50 mM sodium acetate buffer after TCA is extracted twice using H20-saturated ether. A radioimmunoassay kit is used to measure the CAMP content.
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| Cell Assay |
In order to perform binding reactions, 60 μg of membranes are incubated with ICI 118,551 at various concentrations and 10 nM [3H]dihydroalprenolol hydrochloride. The binding reactions are stopped by quickly filtering the mixture through glass fiber filters following a two-hour incubation period at room temperature. Then, using a liquid scintillation counter, the radioactivity in the filters is measured. The presence of 1 μM alprenolol is used to determine non-specific binding. GraphPad Prism is used to analyze binding data.
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| References |
| Molecular Formula |
C17H28CLNO2
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|---|---|
| Molecular Weight |
313.8627
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| Exact Mass |
313.18
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| Elemental Analysis |
C, 65.06; H, 8.99; Cl, 11.29; N, 4.46; O, 10.19
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| CAS # |
72795-01-8
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| Related CAS # |
Zenidolol; 72795-26-7; 91021-57-7 (racemic)
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| Appearance |
White to off-white solid powder
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| tPSA |
41.5Ų
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| SMILES |
CC1=C2CCCC2=C(C=C1)OC[C@@H]([C@H](C)NC(C)C)O.Cl
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| InChi Key |
KBXMBGWSOLBOQM-LINSIKMZSA-N
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| InChi Code |
InChI=1S/C17H27NO2.ClH/c1-11(2)18-13(4)16(19)10-20-17-9-8-12(3)14-6-5-7-15(14)17;/h8-9,11,13,16,18-19H,5-7,10H2,1-4H3;1H/t13-,16-;/m0./s1
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| Chemical Name |
(2R,3S)-1-[(7-methyl-2,3-dihydro-1H-inden-4-yl)oxy]-3-(propan-2-ylamino)butan-2-ol;hydrochloride
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| Synonyms |
ICI118551; ICI118,551; ICI 118,551; ICI 118551; ICI-118551;ICI-118,551; ICI-118551 HCl
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 33.3~62 mg/mL (106.2~197.5 mM)
Ethanol: ~62 mg/mL Water: ~21 mg/mL |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1861 mL | 15.9307 mL | 31.8613 mL | |
| 5 mM | 0.6372 mL | 3.1861 mL | 6.3723 mL | |
| 10 mM | 0.3186 mL | 1.5931 mL | 3.1861 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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