PD-156707 | CAS#162412-70-6 | Endothelin A Receptor Antagonist

MedKoo Cat#: 532448 | Name: PD-156707

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

PD-156707 is an endothelin A receptor-selective antagonist. PD 156707 showed specific binding to target receptors in the myocardium but high accumulation in bile and intestine

Chemical Structure

PD-156707

CAS#162412-70-6

Theoretical Analysis

MedKoo Cat#: 532448

Name: PD-156707

CAS#: 162412-70-6

Chemical Formula: C28H25NaO9

Exact Mass: 528.1396

Molecular Weight: 528.49

Elemental Analysis: C, 63.64; H, 4.77; Na, 4.35; O, 27.25

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 500.00	2 Weeks
25mg	USD 950.00	2 Weeks

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Related CAS #

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Synonym

PD-156707; PD 156707; PD156707.

IUPAC/Chemical Name

sodium (Z)-2-(1,3-benzodioxol-5-yl)-4-(4-methoxyphenyl)-4-oxo-3-[(3,4,5-trimethoxyphenyl)methyl]but-2-enoate

InChi Key

ZLHQEGFYBMZQGM-RKVLWQGQSA-M

InChi Code

InChI=1S/C28H26O9.Na/c1-32-19-8-5-17(6-9-19)26(29)20(11-16-12-23(33-2)27(35-4)24(13-16)34-3)25(28(30)31)18-7-10-21-22(14-18)37-15-36-21;/h5-10,12-14H,11,15H2,1-4H3,(H,30,31);/q;+1/p-1/b25-20-;

SMILES Code

O=C([O-])/C(C1=CC=C(OCO2)C2=C1)=C(CC3=CC(OC)=C(OC)C(OC)=C3)\C(C4=CC=C(OC)C=C4)=O.[Na+]

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

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

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot# S8G10M18

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

PD-156707 is an endothelin A receptor-selective antagonist.

In vitro activity:

PD156707 (Parke-Davis) is one of a series of novel, orally-active butenolide endothelin antagonists and is highly selective for the ETA receptor. PD156707 exhibits subnanomolar affinity and greater than 1000-fold selectivity for human ETA receptors and potently inhibits ET-1-mediated vasoconstriction in human isolated blood vessels. Reference: Expert Opin Investig Drugs. 1999 Jan;8(1):71-8. https://pubmed.ncbi.nlm.nih.gov/15992060/

In vivo activity:

Newborn rats were exposed to anoxia twice daily from postnatal day 1 to 3, and hearts were isolated and studied at postnatal day 4 (P4), 7 (P7), and 14 (P14). Newborn administration of PD156707, an ETA-receptor antagonist, significantly increased cardiomyocyte proliferation at P4 and cell size at P7, resulting in an increase in the heart to body weight ratio in P7 neonates. In addition, PD156707 abrogated the anoxia-mediated effects. Reference: PLoS One. 2015 Feb 18;10(2):e0116600. https://pubmed.ncbi.nlm.nih.gov/25692855/

Preparing Stock Solutions

The following data is based on the product molecular weight 528.49 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

Formulation protocol:

1. Maguire JJ, Davenport AP. The therapeutic potential of PD156707 and related butenolide endothelin antagonists. Expert Opin Investig Drugs. 1999 Jan;8(1):71-8. doi: 10.1517/13543784.8.1.71. PMID: 15992060. 2. Harland SP, Kuc RE, Pickard JD, Davenport AP. Expression of endothelin(A) receptors in human gliomas and meningiomas, with high affinity for the selective antagonist PD156707. Neurosurgery. 1998 Oct;43(4):890-8; discussion 898-9. doi: 10.1097/00006123-199810000-00097. PMID: 9766317. 3. Paradis AN, Gay MS, Wilson CG, Zhang L. Newborn hypoxia/anoxia inhibits cardiomyocyte proliferation and decreases cardiomyocyte endowment in the developing heart: role of endothelin-1. PLoS One. 2015 Feb 18;10(2):e0116600. doi: 10.1371/journal.pone.0116600. PMID: 25692855; PMCID: PMC4334650. 4. Wedgwood S, McMullan DM, Bekker JM, Fineman JR, Black SM. Role for endothelin-1-induced superoxide and peroxynitrite production in rebound pulmonary hypertension associated with inhaled nitric oxide therapy. Circ Res. 2001 Aug 17;89(4):357-64. doi: 10.1161/hh1601.094983. PMID: 11509453.

In vitro protocol:

In vivo protocol:

1. Paradis AN, Gay MS, Wilson CG, Zhang L. Newborn hypoxia/anoxia inhibits cardiomyocyte proliferation and decreases cardiomyocyte endowment in the developing heart: role of endothelin-1. PLoS One. 2015 Feb 18;10(2):e0116600. doi: 10.1371/journal.pone.0116600. PMID: 25692855; PMCID: PMC4334650. 2. Wedgwood S, McMullan DM, Bekker JM, Fineman JR, Black SM. Role for endothelin-1-induced superoxide and peroxynitrite production in rebound pulmonary hypertension associated with inhaled nitric oxide therapy. Circ Res. 2001 Aug 17;89(4):357-64. doi: 10.1161/hh1601.094983. PMID: 11509453.

1: Kimm MA, Haas H, Stölting M, Kuhlmann M, Geyer C, Glasl S, Schäfers M, Ntziachristos V, Wildgruber M, Höltke C. Targeting Endothelin Receptors in a Murine Model of Myocardial Infarction Using a Small Molecular Fluorescent Probe. Mol Pharm. 2020 Jan 6;17(1):109-117. doi: 10.1021/acs.molpharmaceut.9b00810. Epub 2019 Dec 18. PMID: 31816245. 2: Paradis AN, Gay MS, Wilson CG, Zhang L. Newborn hypoxia/anoxia inhibits cardiomyocyte proliferation and decreases cardiomyocyte endowment in the developing heart: role of endothelin-1. PLoS One. 2015 Feb 18;10(2):e0116600. doi: 10.1371/journal.pone.0116600. PMID: 25692855; PMCID: PMC4334650. 3: Yokoyama Y, Osano A, Hayashi H, Itoh K, Okura T, Deguchi Y, Ito Y, Yamada S. Endothelin-1 receptors in rat tissues: characterization by bosentan, ambrisentan and CI-1020. Biol Pharm Bull. 2014;37(3):461-5. doi: 10.1248/bpb.b13-00881. PMID: 24583865. 4: Büther K, Compeer MG, De Mey JG, Schober O, Schäfers M, Bremer C, Riemann B, Höltke C. Assessment of endothelin-A receptor expression in subcutaneous and orthotopic thyroid carcinoma xenografts in vivo employing optical imaging methods. Endocrinology. 2012 Jun;153(6):2907-18. doi: 10.1210/en.2011-2017. Epub 2012 Apr 17. PMID: 22510270. 5: Compeer MG, Meens MJ, Hackeng TM, Neugebauer WA, Höltke C, De Mey JG. Agonist-dependent modulation of arterial endothelinA receptor function. Br J Pharmacol. 2012 Jul;166(6):1833-45. doi: 10.1111/j.1476-5381.2012.01896.x. PMID: 22324472; PMCID: PMC3402808. 6: Lohsiriwat V, Scholefield JH, Dashwood MR, Wilson VG. Pharmacological characteristics of endothelin receptors on sheep rectal blood vessels. Pharmacol Res. 2011 Jun;63(6):490-5. doi: 10.1016/j.phrs.2011.02.010. Epub 2011 Mar 5. PMID: 21382493. 7: Michel K, Büther K, Law MP, Wagner S, Schober O, Hermann S, Schäfers M, Riemann B, Höltke C, Kopka K. Development and evaluation of endothelin-A receptor (radio)ligands for positron emission tomography. J Med Chem. 2011 Feb 24;54(4):939-48. doi: 10.1021/jm101110w. Epub 2011 Jan 28. PMID: 21275367. 8: Peng HJ, Dai DZ, Ji H, Dai Y. The separate roles of endothelin receptors participate in remodeling of matrix metalloproteinase and connexin 43 of cardiac fibroblasts in maladaptive response to isoproterenol. Eur J Pharmacol. 2010 May 25;634(1-3):101-6. doi: 10.1016/j.ejphar.2010.02.001. Epub 2010 Feb 16. PMID: 20167215. 9: Höltke C, Law MP, Wagner S, Kopka K, Faust A, Breyholz HJ, Schober O, Bremer C, Riemann B, Schäfers M. PET-compatible endothelin receptor radioligands: synthesis and first in vitro and in vivo studies. Bioorg Med Chem. 2009 Oct 15;17(20):7197-208. doi: 10.1016/j.bmc.2009.08.058. Epub 2009 Sep 2. PMID: 19766010. 10: Höltke C, von Wallbrunn A, Kopka K, Schober O, Heindel W, Schäfers M, Bremer C. A fluorescent photoprobe for the imaging of endothelin receptors. Bioconjug Chem. 2007 May-Jun;18(3):685-94. doi: 10.1021/bc060264w. Epub 2007 Apr 7. PMID: 17417816. 11: Höltke C, Law MP, Wagner S, Breyholz HJ, Kopka K, Bremer C, Levkau B, Schober O, Schäfers M. Synthesis, in vitro pharmacology and biodistribution studies of new PD 156707-derived ET(A) receptor radioligands. Bioorg Med Chem. 2006 Mar 15;14(6):1910-7. doi: 10.1016/j.bmc.2005.10.039. Epub 2005 Nov 10. PMID: 16289856. 12: Wiley KE, Davenport AP. Endothelin receptor pharmacology and function in the mouse: comparison with rat and man. J Cardiovasc Pharmacol. 2004 Nov;44 Suppl 1:S4-6. doi: 10.1097/01.fjc.0000166204.89426.20. PMID: 15838332. 13: Lee JW, Gonzalez RF, Chapin CJ, Busch J, Fineman JR, Gutierrez JA. Nitric oxide decreases surfactant protein gene expression in primary cultures of type II pneumocytes. Am J Physiol Lung Cell Mol Physiol. 2005 May;288(5):L950-7. doi: 10.1152/ajplung.00210.2004. Epub 2005 Jan 7. PMID: 15640287. 14: Fratz S, Meyrick B, Ovadia B, Johengen MJ, Reinhartz O, Azakie A, Ross G, Fitzgerald R, Oishi P, Hess J, Black SM, Fineman JR. Chronic endothelin A receptor blockade in lambs with increased pulmonary blood flow and pressure. Am J Physiol Lung Cell Mol Physiol. 2004 Sep;287(3):L592-7. doi: 10.1152/ajplung.00093.2004. Epub 2004 May 21. PMID: 15155268. 15: Fellner SK, Arendshorst WJ. Endothelin A and B receptors of preglomerular vascular smooth muscle cells. Kidney Int. 2004 May;65(5):1810-7. doi: 10.1111/j.1523-1755.2004.00579.x. PMID: 15086921. 16: Langleben D. Clinical relevance of endothelin B-mediated vasoconstriction in lambs with increased pulmonary blood flow. Circulation. 2004 Apr 13;109(14):e183; author reply e183. doi: 10.1161/01.CIR.0000124886.51828.E6. PMID: 15078812. 17: Black SM, Mata-Greenwood E, Dettman RW, Ovadia B, Fitzgerald RK, Reinhartz O, Thelitz S, Steinhorn RH, Gerrets R, Hendricks-Munoz K, Ross GA, Bekker JM, Johengen MJ, Fineman JR. Emergence of smooth muscle cell endothelin B-mediated vasoconstriction in lambs with experimental congenital heart disease and increased pulmonary blood flow. Circulation. 2003 Sep 30;108(13):1646-54. doi: 10.1161/01.CIR.0000087596.01416.2F. Epub 2003 Sep 8. PMID: 12963646. 18: Momma K, Nakanishi T, Imamura S. Inhibition of in vivo constriction of fetal ductus arteriosus by endothelin receptor blockade in rats. Pediatr Res. 2003 Mar;53(3):479-85. doi: 10.1203/01.PDR.0000049516.70216.2E. PMID: 12595598. 19: Xu H, Lin L, Yuan WJ. Antiarrhythmic effect of endothelin-A receptor antagonist on acute ischemic arrhythmia in isolated rat heart. Acta Pharmacol Sin. 2003 Jan;24(1):37-44. PMID: 12511227. 20: Maguire JJ, Yu JC, Davenport AP. ETA receptor antagonists inhibit intimal smooth muscle cell proliferation in human vessels. Clin Sci (Lond). 2002 Aug;103 Suppl 48:184S-188S. doi: 10.1042/CS103S184S. PMID: 12193082.