Synonym
Belfosdil; BMY 21891; BMY-21891; BMY21891; SR 7037; SR7037; SR-7037;
IUPAC/Chemical Name
Phosphonic acid, (2-(2-phenoxyethyl)-1,3-propanediyl)bis-, tetrabutyl ester
InChi Key
QTBMDDQRDDABNC-UHFFFAOYSA-N
InChi Code
InChI=1S/C27H50O7P2/c1-5-9-19-31-35(28,32-20-10-6-2)24-26(18-23-30-27-16-14-13-15-17-27)25-36(29,33-21-11-7-3)34-22-12-8-4/h13-17,26H,5-12,18-25H2,1-4H3
SMILES Code
O=P(CC(CCOC1=CC=CC=C1)CP(OCCCC)(OCCCC)=O)(OCCCC)OCCCC
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
Biological target:
Belfosdil is an antihypertensive calcium channel blocker.
In vitro activity:
Glucose and KCl, which depolarize the cell membrane, as well as the Ca2+-mobilizing agonist, carbachol (CCh), cause substantial increases in [Ca2+]m which are associated with smaller rises in [Ca2+]c. The L-type Ca2+-channel blocker, SR7037, abolished the effects of glucose and KCl while attenuating the CCh response.
Reference: J Clin Invest. 1996 Dec 1;98(11):2524-38. https://pubmed.ncbi.nlm.nih.gov/8958215/
In vivo activity:
Purified rat beta-cells were attached to this matrix and incubated under various conditions known to affect [Ca2+]i. The effect of glucose on beta-cell spreading was mimicked by 25 mmol/l KCl (which induces calcium influx) and inhibited by diazoxide (which impairs depolarization and calcium entry) and by the L-type Ca2+ channel blocker SR-7037.
Reference: Diabetes. 2001 May;50(5):1039-46. https://pubmed.ncbi.nlm.nih.gov/11334406/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
548.64
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. Kennedy ED, Rizzuto R, Theler JM, Pralong WF, Bastianutto C, Pozzan T, Wollheim CB. Glucose-stimulated insulin secretion correlates with changes in mitochondrial and cytosolic Ca2+ in aequorin-expressing INS-1 cells. J Clin Invest. 1996 Dec 1;98(11):2524-38. doi: 10.1172/JCI119071. PMID: 8958215; PMCID: PMC507710.
2. Rutter GA, Theler JM, Murgia M, Wollheim CB, Pozzan T, Rizzuto R. Stimulated Ca2+ influx raises mitochondrial free Ca2+ to supramicromolar levels in a pancreatic beta-cell line. Possible role in glucose and agonist-induced insulin secretion. J Biol Chem. 1993 Oct 25;268(30):22385-90. PMID: 8226749.
3. Bosco D, Gonelle-Gispert C, Wollheim CB, Halban PA, Rouiller DG. Increased intracellular calcium is required for spreading of rat islet beta-cells on extracellular matrix. Diabetes. 2001 May;50(5):1039-46. doi: 10.2337/diabetes.50.5.1039. PMID: 11334406.
In vitro protocol:
1. Kennedy ED, Rizzuto R, Theler JM, Pralong WF, Bastianutto C, Pozzan T, Wollheim CB. Glucose-stimulated insulin secretion correlates with changes in mitochondrial and cytosolic Ca2+ in aequorin-expressing INS-1 cells. J Clin Invest. 1996 Dec 1;98(11):2524-38. doi: 10.1172/JCI119071. PMID: 8958215; PMCID: PMC507710.
2. Rutter GA, Theler JM, Murgia M, Wollheim CB, Pozzan T, Rizzuto R. Stimulated Ca2+ influx raises mitochondrial free Ca2+ to supramicromolar levels in a pancreatic beta-cell line. Possible role in glucose and agonist-induced insulin secretion. J Biol Chem. 1993 Oct 25;268(30):22385-90. PMID: 8226749.
In vivo protocol:
1. Bosco D, Gonelle-Gispert C, Wollheim CB, Halban PA, Rouiller DG. Increased intracellular calcium is required for spreading of rat islet beta-cells on extracellular matrix. Diabetes. 2001 May;50(5):1039-46. doi: 10.2337/diabetes.50.5.1039. PMID: 11334406.
1: Bosco D, Gonelle-Gispert C, Wollheim CB, Halban PA, Rouiller DG. Increased intracellular calcium is required for spreading of rat islet beta-cells on extracellular matrix. Diabetes. 2001 May;50(5):1039-46. PubMed PMID: 11334406.
2: Rutter GA, Theler JM, Murgia M, Wollheim CB, Pozzan T, Rizzuto R. Stimulated Ca2+ influx raises mitochondrial free Ca2+ to supramicromolar levels in a pancreatic beta-cell line. Possible role in glucose and agonist-induced insulin secretion. J Biol Chem. 1993 Oct 25;268(30):22385-90. PubMed PMID: 8226749.
3: Mulvana DE, Kaul S, Dandekar KA, Pittman KA. Determination of belfosdil, a new calcium channel blocker, in human plasma by capillary gas chromatography with nitrogen-phosphorus detection. J Chromatogr. 1990 May 18;527(2):343-50. PubMed PMID: 2387881.
4: Kennedy ED, Rizzuto R, Theler JM, Pralong WF, Bastianutto C, Pozzan T, Wollheim CB. Glucose-stimulated insulin secretion correlates with changes in mitochondrial and cytosolic Ca2+ in aequorin-expressing INS-1 cells. J Clin Invest. 1996 Dec 1;98(11):2524-38. PubMed PMID: 8958215; PubMed Central PMCID: PMC507710.
5: Li G, Hidaka H, Wollheim CB. Inhibition of voltage-gated Ca2+ channels and insulin secretion in HIT cells by the Ca2+/calmodulin-dependent protein kinase II inhibitor KN-62: comparison with antagonists of calmodulin and L-type Ca2+ channels. Mol Pharmacol. 1992 Sep;42(3):489-8. PubMed PMID: 1328847.
6: Rossier JR, Cox JA, Niesor EJ, Bentzen CL. A new class of calcium entry blockers defined by 1,3-diphosphonates. Interactions of SR-7037 (belfosdil) with receptors for calcium channel ligands. J Biol Chem. 1989 Oct 5;264(28):16598-607. PubMed PMID: 2550449.
