 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C28H26O9 |
| Molecular Weight | 506.50064 |
| Exact Mass | 506.158 |
| CAS # | 162256-50-0 |
| PubChem CID | 9870830 |
| Appearance | Typically exists as solid at room temperature |
| Density | 1.351g/cm3 |
| Boiling Point | 722.338ºC at 760 mmHg |
| Flash Point | 242.505ºC |
| Vapour Pressure | 0mmHg at 25°C |
| Index of Refraction | 1.623 |
| LogP | 3.848 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 37 |
| Complexity | 824 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O1C2C=CC(C3=C(CC4C=C(OC)C(OC)=C(OC)C=4)C(O)(C4C=CC(OC)=CC=4)OC3=O)=CC=2OC1 |
| InChi Key | PWIPORDFWDZCJG-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C28H26O9/c1-31-19-8-6-18(7-9-19)28(30)20(11-16-12-23(32-2)26(34-4)24(13-16)33-3)25(27(29)37-28)17-5-10-21-22(14-17)36-15-35-21/h5-10,12-14,30H,11,15H2,1-4H3 |
| Chemical Name | 3-(1,3-benzodioxol-5-yl)-5-hydroxy-5-(4-methoxyphenyl)-4-[(3,4,5-trimethoxyphenyl)methyl]furan-2-one |
| Synonyms | 162256-50-0; CI 1020; 3-Benzo[1,3]dioxol-5-yl-5-hydroxy-5-(4-methoxy-phenyl)-4-(3,4,5-trimethoxy-benzyl)-5H-furan-2-one; PD156707; CHEMBL8981; 3-(1,3-benzodioxol-5-yl)-5-hydroxy-5-(4-methoxyphenyl)-4-[(3,4,5-trimethoxyphenyl)methyl]furan-2-one; CI1020-d9; CI1020; |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | ETA 0.3 nM (IC50) |
| ln Vitro |
In organ culture, CI-1020 (1 μM, 28 days) totally prevents human saphenous vein intimal hyperplasia [1]. Tissues cannot be harmed by CI-1020 (1 μM, 14 days) [1]. Researchers have determined the ability of the endothelin (ET)(A) receptor antagonist, PD156707 (CI 1020), to inhibit intimal proliferation in human saphenous veins maintained in organ culture. After 28 days in culture, veins exposed to 1 microM PD156707 exhibited a significant reduction in intima to intima-plus-media ratio (I:I+M ratio) (0.14+/-0.02, n=15) and an increase in lumen area (3.1+/-0.8 mm(2)) compared with veins cultured without the antagonist (I:I+M, 0.29+/-0.02; lumen area, 2.5+/-0.7 mm(2); n=23) but were not significantly different from pre-cultured controls (I:I+M, 0.15+/-0.02; lumen area, 4.4+/-1.2 mm(2); n=17) (Dunn's test for non-parametric multiple comparisons: alpha<0.05). In organ bath experiments, ET-1 and 5-hydroxytryptamine constricted pre-cultured control vessels with pD(2) values (where pD(2) is defined as the negative logarithm of the molar EC(50) value of an agonist) of 8.9+/-0.4 and 7.0+/-0.4 (n=3) and E(max) (efficacy) values of 86+/-3% and 71+/-13% (compared with constriction induced by KCl) respectively. There was no difference in the responsiveness of veins cultured for 14 days to either agonist, indicating that the vessels maintained in organ culture remain viable. Crucially, vein segments cultured with 1 microM PD156707 (a concentration that antagonized ET-1 responses in pre-cultured control vessels) contracted to ET-1 with a potency comparable to that obtained in vessels cultured in the absence of the antagonist (pD(2)=8.9+/-0.4 and 8.0+/-0.6 respectively, n=3) confirming that PD156707 was not toxic to the tissue at the concentration used. In conclusion we have shown that the ET(A)-selective antagonist, PD156707, completely blocked intimal hyperplasia in human saphenous veins in organ culture, suggesting that ET(A) antagonists may be beneficial in preventing or delaying saphenous vein graft disease in patients receiving bypass grafts for coronary artery disease[1]. |
| ln Vivo |
ET-A is totally inhibited by CI-1020 (30 mg/kg, po), and the basal blood pressure of normal rats is unaffected[2]. In rats subjected to prolonged hypoxia, CI-1020f (40 mg/kg, po) reduces established pulmonary hypertension[4].
The mechanism of Hypoxic Pulmonary Vasoconstriction is unknown. The role of endothelin-1 in hypoxic pulmonary vasoconstriction was studied in precontracted small and large pulmonary arteries using the endothelin ETA receptor antagonist sodium-2-benzol [1,3]dioxol-5-yl-4-(4-methoxyphenyl)-4-oxo-3-(3,4,5-trimethoxy-ben zyl)-but-2-enoate (CI-1020). Small rat pulmonary arteries exhibit a mixed endothelin ETA receptor and endothelin ETB2 receptor population whereas large rat pulmonary arteries contain only endothelin ETA receptors. CI-1020 inhibited endothelin-1 in small vessels via endothelin ETA receptor blockade (1 and 10 microM) and at high concentrations via endothelin ETA receptor and endothelin ETB2 receptor blockade (100 microM). CI-1020 (0.01, 0.1 and 1 microM) inhibited endothelin-1 in large vessels via endothelin ETA receptor blockade alone. CI-1020 (1, 10 and 100 microM) significantly reduced hypoxic pulmonary vasoconstriction in small vessels, by -9.8+/-1.4, -9.2+/-2.3 and -8.0+/-1.7% 80 mM K+, respectively, compared to +2.5+/-4.2% with vehicle (P < 0.05). CI-1020 (0.01, 0.1 and 1 microM) had no significant effect upon hypoxic pulmonary vasoconstriction in large vessels. In small, but not large, pulmonary arteries hypoxic pulmonary vasoconstriction is due in part to the action of endothelin-1 at the endothelin ETA receptor.[3] ETA receptor antagonists have previously been shown to prevent the development of pulmonary hypertension induced by chronic hypoxia in the rat. Clinically, however, patients present with already established pulmonary hypertension. Researchers have investigated the effects of the ETA receptor antagonist CI-1020 in rats previously adapted to chronic hypoxia. Two protocols were followed. Rats (n=32) were divided into two batches of four groups: normoxic controls in air for 10 days (NC10), chronic hypoxic controls in hypoxia for 10 days (CHC10), chronic hypoxic vehicle treated in hypoxia for 20 days (CHV20) and chronic hypoxic drug treated in hypoxia for 20 days (CHT20). Ten days after the onset of hypoxia, oral treatment with drug (40 mg/kg per day) or vehicle was started. Animal weight, ratio of right ventricular weight to left ventricular weight including septum (RV/LV+S) and percentage of double elastic lamina (DEL) were determined. In the second study, 12 rats were divided into three groups; normoxic controls in air for 20 days (NC20), (CHV20) and (CHT20). After 10 days hypoxia, oral treatment with drug (40 mg/kg per day) or vehicle was started. Isolated perfused lung preparations were then used to determine pulmonary artery pressure and pulmonary vascular resistance. Treatment with CI-1020 reduced the increase in RV/LV+S and the percentage DEL induced by chronic hypoxia and significantly lowered the increase in pulmonary resistance in isolated perfused lungs from chronically hypoxic animals. These results suggest that CI-1020 could have an important role in the treatment and reversal of established pulmonary vascular remodelling[4]. |
| Animal Protocol |
Animal/Disease Models: normal rats[2] Doses: 30 mg/kg Route of Administration: oral administration (po) Experimental Results: Inhibited the ET-A and has no significant effect on basal blood pressure in normotensive rats. Animal/Disease Models: basal blood pressure in normotensive rats[4] Doses: 40 mg/kg/day Route of Administration: oral administration (po) Experimental Results: decreased the increase in RV/LV+S and the percentage DEL induced by chronic hypoxia. Lowered the increase in pulmonary resistance in isolated perfused lungs Dramatically. |
| References |
[1]. ETA receptor antagonists inhibit intimal smooth muscle cell proliferation in human vessels. Clin Sci (Lond). 2002 Aug;103 Suppl 48:184S-188S. [2]. Discovery and development of an endothelin A receptor-selective antagonist PD 156707. Pharm Biotechnol. 1998;11:81-112. [3]. The effect of the endothelin ET(A) receptor antagonist CI-1020 on hypoxic pulmonary vasoconstriction. Eur J Pharmacol. 1999 Jun 25;374(3):367-75. [4]. The effect of the ETA receptor antagonist (CI-1020) in rats with established hypoxic pulmonary hypertension. Pulm Pharmacol Ther. 1998 Apr-Jun;11(2-3):173-6. |
| Additional Infomation | PD 156707 is a highly potent, selective antagonist of the ETA receptor that has demonstrated efficacy in a number of different disease models. The next few years will be exciting in the field of ET research as several compounds progress through clinical development. It is our hope that the efficacy that data demonstrated to date with PD 156707 will some day be translated into real hope for the patients who are waiting beyond the confines of our research laboratories.[2] |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9743 mL | 9.8717 mL | 19.7433 mL | |
| 5 mM | 0.3949 mL | 1.9743 mL | 3.9487 mL | |
| 10 mM | 0.1974 mL | 0.9872 mL | 1.9743 mL |