WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 319815
CAS#: 340021-17-2
Description: Tonapofylline, also known as BG9928, is a selective adenosine-1 receptor antagonist under development for the treatment of heart failure. Tonapofylline promotes natriuresis and diuresis, and may preserve glomerular filtration rate in patients with heart failure. Additionally, pilot data indicate that tonapofylline may be renoprotective in the setting of concomitant treatment with a loop-diuretic. Tonapofylline has natriuretic effects and is able to maintain renal function, which can be beneficial to patients with congestive heart failure.
MedKoo Cat#: 319815
Name: Tonapofylline
CAS#: 340021-17-2
Chemical Formula: C22H32N4O4
Exact Mass: 416.2424
Molecular Weight: 416.522
Elemental Analysis: C, 63.44; H, 7.74; N, 13.45; O, 15.36
Synonym: BG9928; BG-9928; BG 9928; Tonapofylline.
IUPAC/Chemical Name: 3-(4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)bicyclo[2.2.2]octan-1-yl)propanoic acid
InChi Key: ZWTVVWUOTJRXKM-UHFFFAOYSA-N
InChi Code: InChI=1S/C22H32N4O4/c1-3-13-25-17-16(18(29)26(14-4-2)20(25)30)23-19(24-17)22-10-7-21(8-11-22,9-12-22)6-5-15(27)28/h3-14H2,1-2H3,(H,23,24)(H,27,28)
SMILES Code: O=C(O)CCC1(CC2)CCC2(C(N3)=NC(N(CCC)C(N4CCC)=O)=C3C4=O)CC1
1: Li Z, Tenhoor C, Marbury T, Swan S, Zhu Y, Ticho B. Pharmacokinetics and pharmacodynamics of tonapofylline in subjects with severe renal impairment and in elderly subjects. Int J Clin Pharmacol Ther. 2011 Sep;49(9):563-70. PubMed PMID: 21888869.
2: Li Z, Gan LS, Marbury T, Lasseter KC, Natarajan A, Stecher S, Wei D, Yang L, Freedman D, Deykin A. Pharmacokinetics of oral tonapofylline and its acyl-glucuronide metabolite in patients with mild and moderate hepatic impairment. J Clin Pharmacol. 2012 Apr;52(4):543-51. doi: 10.1177/0091270011400413. Epub 2011 May 24. PubMed PMID: 21610206.
3: Gottlieb SS, Ticho B, Deykin A, Abraham WT, Denofrio D, Russell SD, Chapman D, Smith W, Goldman S, Thomas I. Effects of BG9928, an adenosine A₁ receptor antagonist, in patients with congestive heart failure. J Clin Pharmacol. 2011 Jun;51(6):899-907. doi: 10.1177/0091270010375957. Epub 2010 Oct 6. PubMed PMID: 20926754.
4: Li Z, TenHoor C, Marbury T, Swan S, Ticho B, Rogge M, Nestorov I. Clinical pharmacokinetics of tonapofylline: evaluation of dose proportionality, oral bioavailability, and gender and food effects in healthy human subjects. J Clin Pharmacol. 2011 Jul;51(7):1004-14. doi: 10.1177/0091270010377633. Epub 2010 Oct 6. PubMed PMID: 20926751.
5: Ensor CR, Russell SD. Tonapofylline: a selective adenosine-1 receptor antagonist for the treatment of heart failure. Expert Opin Pharmacother. 2010 Oct;11(14):2405-15. doi: 10.1517/14656566.2010.514605. Review. PubMed PMID: 20807184.
6: Gill A, Wortham K, Costa D, Davis W, Ticho B, Whalley E. Protective effect of tonapofylline (BG9928), an adenosine A1 receptor antagonist, against cisplatin-induced acute kidney injury in rats. Am J Nephrol. 2009;30(6):521-6. doi: 10.1159/000248762. Epub 2009 Oct 13. PubMed PMID: 19828940.
7: Kiesman WF, Elzein E, Zablocki J. A1 adenosine receptor antagonists, agonists, and allosteric enhancers. Handb Exp Pharmacol. 2009;(193):25-58. doi: 10.1007/978-3-540-89615-9_2. Review. PubMed PMID: 19639278.
8: Dohadwala MM, Givertz MM. Role of adenosine antagonism in the cardiorenal syndrome. Cardiovasc Ther. 2008 Winter;26(4):276-86. doi: 10.1111/j.1755-5922.2008.00059.x. Review. PubMed PMID: 19035879.
9: Bayés M, Rabasseda X. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2008 Jan-Feb;30(1):67-99. PubMed PMID: 18389098.
10: Greenberg B, Thomas I, Banish D, Goldman S, Havranek E, Massie BM, Zhu Y, Ticho B, Abraham WT. Effects of multiple oral doses of an A1 adenosine antagonist, BG9928, in patients with heart failure: results of a placebo-controlled, dose-escalation study. J Am Coll Cardiol. 2007 Aug 14;50(7):600-6. Epub 2007 Jul 30. PubMed PMID: 17692744.
11: Kiesman WF, Zhao J, Conlon PR, Dowling JE, Petter RC, Lutterodt F, Jin X, Smits G, Fure M, Jayaraj A, Kim J, Sullivan G, Linden J. Potent and orally bioavailable 8-bicyclo[2.2.2]octylxanthines as adenosine A1 receptor antagonists. J Med Chem. 2006 Nov 30;49(24):7119-31. PubMed PMID: 17125264.
12: Doggrell SA. BG-9928 (Biogen Idec). Curr Opin Investig Drugs. 2005 Sep;6(9):962-8. PubMed PMID: 16187697.
13: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2004 Jan-Feb;26(1):53-84. Review. PubMed PMID: 14988742.
14: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2003 Dec;25(10):831-55. PubMed PMID: 14735233.
15: Auchampach JA, Jin X, Moore J, Wan TC, Kreckler LM, Ge ZD, Narayanan J, Whalley E, Kiesman W, Ticho B, Smits G, Gross GJ. Comparison of three different A1 adenosine receptor antagonists on infarct size and multiple cycle ischemic preconditioning in anesthetized dogs. J Pharmacol Exp Ther. 2004 Mar;308(3):846-56. Epub 2003 Nov 21. PubMed PMID: 14634049.
