WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 526692
CAS#: 195529-54-5
Description: A-192621 is an endothelin-B antagonist. A-192621 markedly enhanced 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.
MedKoo Cat#: 526692
Name: A-192621
CAS#: 195529-54-5
Chemical Formula: C33H38N2O6
Exact Mass: 558.273
Molecular Weight: 558.675
Elemental Analysis: C, 70.95; H, 6.86; N, 5.01; O, 17.18
Synonym: A-192621; A 192621; A192621; A-192621-1; A-192621.1.
IUPAC/Chemical Name: (2R,3R,4S)-4-(benzo[d][1,3]dioxol-5-yl)-1-(2-((2,6-diethylphenyl)amino)-2-oxoethyl)-2-(4-propoxyphenyl)pyrrolidine-3-carboxylic acid
InChi Key: LQEHCKYYIXQEBM-FUKIBTTHSA-N
InChi Code: InChI=1S/C33H38N2O6/c1-4-16-39-25-13-10-23(11-14-25)32-30(33(37)38)26(24-12-15-27-28(17-24)41-20-40-27)18-35(32)19-29(36)34-31-21(5-2)8-7-9-22(31)6-3/h7-15,17,26,30,32H,4-6,16,18-20H2,1-3H3,(H,34,36)(H,37,38)/t26-,30-,32+/m1/s1
SMILES Code: 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
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
The following data is based on the product molecular weight 558.675 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
1: Brodsky S, Abassi Z, Wessale J, Ramadan R, Winaver J, Hoffman A. Effects of A-192621.1, a specific endothelin-B antagonist, on intrarenal hemodynamic responses to endothelin-1. J Cardiovasc Pharmacol. 2000 Nov;36(5 Suppl 1):S311-3. doi: 10.1097/00005344-200036051-00090. PMID: 11078406.
2: Wu-Wong JR, Dixon DB, Chiou WJ, Sorensen BK, Liu G, Jae HS, Tasker A, von Geldern TW, Winn M, Opgenorth TJ. 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. doi: 10.1042/CS103S107S. PMID: 12193066.
3: Leung SW, Lim SL, Pang CC, Man RY. Use of A-192621 and IRL-2500 to unmask the mesenteric and renal vasodilator role of endothelin ET(B) receptors. J Cardiovasc Pharmacol. 2002 Apr;39(4):533-43. doi: 10.1097/00005344-200204000-00009. PMID: 11904527.
4: Wessale JL, Adler AL, Novosad EI, Calzadilla SV, Dayton BD, Marsh KC, Winn M, Jae HS, von Geldern TW, Opgenorth TJ, Wu-Wong JR. 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. doi: 10.1042/CS103S112S. PMID: 12193067.
5: Cullen JP, Bell D, Kelso EJ, McDermott BJ. Use of A-192621 to provide evidence for involvement of endothelin ET(B)-receptors in endothelin-1-mediated cardiomyocyte hypertrophy. Eur J Pharmacol. 2001 Apr 13;417(3):157-68. doi: 10.1016/s0014-2999(01)00905-0. PMID: 11334846.
6: Wang Y, Wang DH. Prevention of endothelin-1-induced increases in blood pressure: role of endogenous CGRP. Am J Physiol Heart Circ Physiol. 2004 Oct;287(4):H1868-74. doi: 10.1152/ajpheart.00241.2004. Epub 2004 Jun 17. PMID: 15205172.
7: Williams JM, Pollock JS, Pollock DM. Arterial pressure response to the antioxidant tempol and ETB receptor blockade in rats on a high-salt diet. Hypertension. 2004 Nov;44(5):770-5. doi: 10.1161/01.HYP.0000144073.42537.06. Epub 2004 Sep 27. PMID: 15452035.
8: Elgebaly MM, Portik-Dobos V, Sachidanandam K, Rychly D, Malcom D, Johnson MH, Ergul A. Differential effects of ET(A) and ET(B) receptor antagonism on oxidative stress in type 2 diabetes. Vascul Pharmacol. 2007 Aug- Sep;47(2-3):125-30. doi: 10.1016/j.vph.2007.05.006. Epub 2007 Jun 6. PMID: 17597010.
9: Montgomery JP, Patterson PH. Endothelin receptor B antagonists decrease glioma cell viability independently of their cognate receptor. BMC Cancer. 2008 Nov 28;8:354. doi: 10.1186/1471-2407-8-354. PMID: 19040731; PMCID: PMC2613414.
10: Matsumura Y, Hashimoto N, Taira S, Kuro T, Kitano R, Ohkita M, Opgenorth TJ, Takaoka M. Different contributions of endothelin-A and endothelin-B receptors in the pathogenesis of deoxycorticosterone acetate-salt-induced hypertension in rats. Hypertension. 1999 Feb;33(2):759-65. doi: 10.1161/01.hyp.33.2.759. PMID: 10024341.
11: Ye DZ, Wang DH. Function and regulation of endothelin-1 and its receptors in salt sensitive hypertension induced by sensory nerve degeneration. Hypertension. 2002 Feb;39(2 Pt 2):673-8. doi: 10.1161/hy0202.103480. PMID: 11882629.
12: Matsumura Y, Taira S, Kitano R, Hashimoto N, Kuro T. Selective antagonism of endothelin ET(A) or ET(B) receptor in renal hemodynamics and function of deoxycorticosterone acetate-salt-induced hypertensive rats. Biol Pharm Bull. 1999 Aug;22(8):858-62. doi: 10.1248/bpb.22.858. Retraction in: Biol Pharm Bull. 2014;37(6):1080. PMID: 10480326.
13: Mulder P, Boujedaini H, Richard V, Derumeaux G, Henry JP, Renet S, Wessale J, Opgenorth T, Thuillez C. Selective endothelin-A versus combined endothelin-A/endothelin-B receptor blockade in rat chronic heart failure. Circulation. 2000 Aug 1;102(5):491-3. doi: 10.1161/01.cir.102.5.491. PMID: 10920058.
14: Fellner SK, Arendshorst W. Endothelin-A and -B receptors, superoxide, and Ca2+ signaling in afferent arterioles. Am J Physiol Renal Physiol. 2007 Jan;292(1):F175-84. doi: 10.1152/ajprenal.00050.2006. Epub 2006 Jun 20. PMID: 16788136.
15: Mikhail M, Vachon PH, D'Orléans-Juste P, Jacques D, Bkaily G. Role of endothelin-1 and its receptors, ETA and ETB, in the survival of human vascular endothelial cells. Can J Physiol Pharmacol. 2017 Oct;95(10):1298-1305. doi: 10.1139/cjpp-2017-0412. Epub 2017 Jul 21. PMID: 28732172.
16: Yamamoto S, Matsumoto N, Kanazawa M, Fujita M, Takaoka M, Gariepy CE, Yanagisawa M, Matsumura Y. Different contributions of endothelin-A and endothelin-B receptors in postischemic cardiac dysfunction and norepinephrine overflow in rat hearts. Circulation. 2005 Jan 25;111(3):302-9. doi: 10.1161/01.CIR.0000153351.86708.F7. Epub 2005 Jan 10. PMID: 15642760.
17: Lee TM, Chang NC, Lin SZ. Inhibition of infarction-induced sympathetic innervation with endothelin receptor antagonism via a PI3K/GSK-3β-dependent pathway. Lab Invest. 2017 Mar;97(3):243-255. doi: 10.1038/labinvest.2016.138. Epub 2016 Dec 19. PMID: 27991911.
18: Eibl G, Forgacs B, Hotz HG, Buhr HJ, Foitzik T. Endothelin A but not endothelin B receptor blockade reduces capillary permeability in severe experimental pancreatitis. Pancreas. 2002 Aug;25(2):e15-20. doi: 10.1097/00006676-200208000-00019. PMID: 12142750.
19: Hoffman A, Abassi ZA, Brodsky S, Ramadan R, Winaver J. Mechanisms of big endothelin-1-induced diuresis and natriuresis : role of ET(B) receptors. Hypertension. 2000 Mar;35(3):732-9. doi: 10.1161/01.hyp.35.3.732. PMID: 10720587.
20: Williams JM, Zhao X, Wang MH, Imig JD, Pollock DM. Peroxisome proliferator- activated receptor-alpha activation reduces salt-dependent hypertension during chronic endothelin B receptor blockade. Hypertension. 2005 Aug;46(2):366-71. doi: 10.1161/01.HYP.0000172755.25382.fc. Epub 2005 Jun 20. PMID: 15967866.
