Tonapofylline
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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.

Chemical Structure

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Tonapofylline
CAS# 340021-17-2
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 319815
Name: Tonapofylline
CAS#: 340021-17-2
Chemical Formula: C22H32N4O4
Exact Mass: 416.24
Molecular Weight: 416.522
Elemental Analysis: C, 63.44; H, 7.74; N, 13.45; O, 15.36

Price and Availability

Size Price Availability Quantity
5mg USD 90 Ready to ship
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1250 Ready to ship
500mg USD 2650 Ready to ship
1g USD 3850 Ready to ship
2g USD 6450 Ready to ship
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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

Appearance: White to off-white 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

More Info:

Biological target: Tonapofylline (BG 9928) is an orally active and selective adenosine A1 receptor antagonist with a Ki of 7.4 nM for human adenosine A1 receptor (hA1).
In vitro activity: TBD
In vivo activity: An important finding of the present study is that BG9928 exerted significant long-term antidiabetic actions in rats with metabolic syndrome. This conclusion is supported by the observations that chronic BG9928 decreased glucosuria, polydipsia, polyuria, and fasting plasma glucose, and improved the oral glucose tolerance test. Compared with the control group, BG9928 also caused a significant gain in body weight, an effect that was unrelated to food or water intake. This too is consistent with an antidiabetic effect of BG9928, because decreased spillage of glucose into the urine would cause weight gain since the calories in glucose would be conserved. Reference: J Pharmacol Exp Ther. 2016 Feb; 356(2): 333–340. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4727158/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 100.0 240.08

Preparing Stock Solutions

The following data is based on the product molecular weight 416.52 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.

Recalculate based on batch purity %
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: TBD
In vitro protocol: TBD
In vivo protocol: 1. Tofovic SP, Salah EM, Smits GJ, Whalley ET, Ticho B, Deykin A, Jackson EK. Dual A1/A2B Receptor Blockade Improves Cardiac and Renal Outcomes in a Rat Model of Heart Failure with Preserved Ejection Fraction. J Pharmacol Exp Ther. 2016 Feb;356(2):333-40. doi: 10.1124/jpet.115.228841. Epub 2015 Nov 19. PMID: 26585572; PMCID: PMC4727158. 2. 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. PMID: 19828940.tonapo

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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.