| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Other Sizes |
| Targets |
Urotensin-II receptor (UT, also known as GPR14). GSK 1562590 is a high-affinity and selective antagonist of the UT receptor. It has a very slow dissociation rate from the receptor, resulting in prolonged pharmacodynamic activity.
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|---|---|
| ln Vitro |
GSK 1562590 is a high-affinity antagonist of the urotensin-II receptor, with pKi values ranging from 9.14 to 9.66 for mammalian recombinant and native UT receptors (mouse, rat, cat, monkey, human). Its slow dissociation from the receptor is its key property, leading to prolonged ex vivo pharmacodynamic activity. A cell-free radioligand binding assay is performed using membrane preparations from Chinese hamster ovary (CHO) cells stably expressing the human UT receptor. The membranes are incubated with [125I]-urotensin-II and varying concentrations of GSK 1562590 hydrochloride to determine the Ki.
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| ln Vivo |
For an in vitro functional assay, CHO-K1 cells stably expressing the human UT receptor are seeded in 96-well plates and loaded with a calcium-sensitive fluorescent dye (e.g., Fluo-4). Cells are pre-incubated with various concentrations of the antagonist, then stimulated with urotensin-II. The reduction in intracellular calcium flux is measured to determine its IC50. In vivo pharmacodynamic studies are conducted in anesthetized rats. GSK 1562590 hydrochloride is administered intravenously (i.v.). Ex vivo binding assays are performed using kidney or heart membranes harvested from the animals at various times post-dose to measure remaining UT receptor occupancy, demonstrating prolonged pharmacodynamic activity.
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| ADME/Pharmacokinetics |
Not reported. The compound is likely administered intravenously in preclinical models. Its slow dissociation kinetics suggest it has a long duration of action. Its molecular formula is C30H30Cl2N4O4·HCl and its molecular weight is 617.95.
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| Toxicity/Toxicokinetics |
Not reported. As a research compound, formal toxicology data is not available. Given its potent and sustained UT antagonism, potential on-target toxicity could include disruptions of cardiovascular and renal homeostasis, as the U-II system is implicated in these functions.
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| References | |
| Additional Infomation |
Urotensin-II (U-II) is one of the most potent vasoconstrictors known, and the UT receptor is a GPCR. The urotensinergic system is implicated in the pathogenesis of hypertension, heart failure, and diabetic nephropathy. GSK 1562590's unique property of slow receptor dissociation distinguishes it from other antagonists and makes it an ideal tool for studying the long-term consequences of UT blockade. Its development helped clarify the role of U-II in cardiovascular pathology.
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| Molecular Formula |
C30H31CL3N4O4
|
|---|---|
| Molecular Weight |
617.95
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| Exact Mass |
616.141
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| CAS # |
1003878-07-6
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| PubChem CID |
46909864
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
8
|
| Heavy Atom Count |
41
|
| Complexity |
910
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| Defined Atom Stereocenter Count |
1
|
| SMILES |
CN([C@@H](CN1CCCC1)C2=CC=C(C=C2)C3=CC(=CC=C3)C(=O)N)C(=O)CN4C(=O)COC5=CC(=C(C=C54)Cl)Cl.Cl
|
| InChi Key |
XTVXEMMIPYMBLL-SNYZSRNZSA-N
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| InChi Code |
InChI=1S/C30H30Cl2N4O4.ClH/c1-34(28(37)17-36-25-14-23(31)24(32)15-27(25)40-18-29(36)38)26(16-35-11-2-3-12-35)20-9-7-19(8-10-20)21-5-4-6-22(13-21)30(33)39;/h4-10,13-15,26H,2-3,11-12,16-18H2,1H3,(H2,33,39);1H/t26-;/m0./s1
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| Chemical Name |
3-[4-[(1R)-1-[[2-(6,7-dichloro-3-oxo-1,4-benzoxazin-4-yl)acetyl]-methylamino]-2-pyrrolidin-1-ylethyl]phenyl]benzamide;hydrochloride
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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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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: ~25 mg/mL (~40.5 mM; with ultrasonication and warming by heating to 60°C)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.05 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.05 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6183 mL | 8.0913 mL | 16.1825 mL | |
| 5 mM | 0.3237 mL | 1.6183 mL | 3.2365 mL | |
| 10 mM | 0.1618 mL | 0.8091 mL | 1.6183 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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