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Purity: ≥98%
A-192621 is an antagonist of endothelin-B. Endothelins (ETs), 21-amino-acid peptides involved in the pathogenesis of various diseases, bind to ET(A) and ET(B) receptors to initiate their effects. A-192621 can markedly enhance MAP, TPR, and mesenteric, and the renal constrictor effects of ET-1. A-192621 was more effective than IRL-2500 in blocking IRL-1620-induced vasoconstriction, but both augmented constrictor responses to ET-1.
| ln Vitro |
In a dose-dependent manner, A-192621 (1-100 μM) treatment for 48 hours dramatically decreased the cell viability of PASMCs [2]. In PASMCs, treatment with A-192621 (1-100 μM; 48 hours) dramatically elevated caspase-3/7 activity and cleaved caspase-3 expression. A-192621 improves the sensitivity of cells to apoptosis caused by doxorubicin treatment and promotes apoptosis in a dose-dependent manner [2].
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| ln Vivo |
Male Sprague-Dawley rats were treated with A-192621 (30-100 mg/kg; PO; daily; for 3 days) to suppress the ETB-mediated S6c-induced dilation and pressor responses. However, the ETA-mediated ET-1-induced pressor response was not inhibited by this treatment, with an ED50 value of 30 mg/kg. In awake normotensive rats, A-192621 alone raises plasma ET-1 levels and arterial blood pressure [3].
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| Cell Assay |
Cell Viability Assay[2]
Cell Types: Pulmonary arterial smooth muscle cells (PASMCs) with Doxorubicin Tested Concentrations: 1 μM, 10 μM, 50 μM, 100 μM Incubation Duration: 72 hrs (hours) Experimental Results: The viability of PASMCs was Dramatically diminished in a dose- dependent manner. Western Blot Analysis[2] Cell Types: Pulmonary arterial smooth muscle cells (PASMCs) with Doxorubicin Tested Concentrations: 1 μM, 10 μM, 100 μM Incubation Duration: 72 hrs (hours) Experimental Results: The caspase-3/7 activity in PASMCs was Dramatically increased in a dose-dependent manner. |
| Animal Protocol |
Animal/Disease Models: Male SD (Sprague-Dawley) rats (250-350 g)[3]
Doses: 30 mg/kg 100 mg/kg Route of Administration: Oral administration; daily; for 3 days Experimental Results: Inhibited both dilatory and pressor responses induced by S6c mediated by ETB with an ED50value of 30 mg/kg. |
| References |
[1]. Wu-Wong JR, et al. Pharmacology of endothelin receptor antagonists ABT-627, ABT-546, A-182086 and A-192621: in vitro studies. Clin Sci (Lond). 2002 Aug;103 Suppl 48:107S-111S.
[2]. Sakai S, et al. Antagonists to endothelin receptor type B promote apoptosis in human pulmonary arterial smooth muscle cells. Life Sci. 2016 Aug 15;159:116-120. [3]. Wessale JL, et al. Pharmacology of endothelin receptor antagonists ABT-627, ABT-546, A-182086 and A-192621: ex vivo and in vivo studies. Clin Sci (Lond). 2002 Aug;103 Suppl 48:112S-117S. |
| Molecular Formula |
C33H38N2O6
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| Molecular Weight |
558.67
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| CAS # |
195529-54-5
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| SMILES |
O=C([ C@H]1[ C@H](C2=CC=C(OCCC)C=C2)N(CC(NC3=C(CC)C=CC=C3CC)=O)C[C@@H]1C4 =CC=C(OCO5)C5=C4)O
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.47 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7900 mL | 8.9498 mL | 17.8997 mL | |
| 5 mM | 0.3580 mL | 1.7900 mL | 3.5799 mL | |
| 10 mM | 0.1790 mL | 0.8950 mL | 1.7900 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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