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Acolbifene (also known as EM-652 and SCH-57068) is a novel, potent and selective estrogen receptor modulator/antatonist (SERM) with a IC50 value of 22±3 nM. Research is currently being done on acolbifene's potential to prevent breast cancer in women who are at high risk of developing the disease. EM-800 (SCH57050) and EM-652 (SCH 57068), the prodrug, which together have the highest known antiestrogen potency. The substance that has the strongest affinity for the estrogen receptor—including estradiol—is EM-652. Compared to ICI 182780, hydroxytamoxifen, raloxifene, droloxifene, and hydroxytoremifene, it has a higher affinity for the ER. Out of all the antiestrogens tested, EM-652 exhibited the strongest inhibitory activity on both ER alpha and ER beta. Additionally, EM-652 was the most effective inhibitor of the percentage of cancer cells that cycled.
Physicochemical Properties
| Molecular Formula | C29H31NO4 |
| Molecular Weight | 457.561 |
| Exact Mass | 457.23 |
| Elemental Analysis | C, 76.12; H, 6.83; N, 3.06; O, 13.99 |
| CAS # | 182167-02-8 |
| Related CAS # | Acolbifene hydrochloride;252555-01-4;(Rac)-Acolbifene;151533-34-5 |
| PubChem CID | 155435 |
| Appearance | Yellow solid powder |
| Boiling Point | 651.5ºC at 760mmHg |
| Flash Point | 347.8ºC |
| LogP | 6.766 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 34 |
| Complexity | 674 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | OC1=CC=C2C(C)=C(C3=CC=C(O)C=C3)[C@H](C4=CC=C(OCCN5CCCCC5)C=C4)OC2=C1 |
| InChi Key | DUYNJNWVGIWJRI-LJAQVGFWSA-N |
| InChi Code | InChI=1S/C29H31NO4/c1-20-26-14-11-24(32)19-27(26)34-29(28(20)21-5-9-23(31)10-6-21)22-7-12-25(13-8-22)33-18-17-30-15-3-2-4-16-30/h5-14,19,29,31-32H,2-4,15-18H2,1H3/t29-/m0/s1 |
| Chemical Name | (2S)-3-(4-hydroxyphenyl)-4-methyl-2-[4-(2-piperidin-1-ylethoxy)phenyl]-2H-chromen-7-ol |
| Synonyms | EM 652; EM652; EM-652; SCH-57068; SCH 57068; SCH57068 |
| 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 | ERα (IC50 = 2 nM); ERβ (IC50 =0.4 nM) |
| ln Vitro |
Acolbifene (ACOL) does not alter the pathways through which cholesterol is synthesised, indicating that its hypocholesterolemic action is mediated by clearance-related receptors[2]. Acolbifene (EM-652) exhibits no agonistic activity on the transcriptional function of ERα and ERβ and inhibits the activation of both ERα and ERβ mediated by estradiol (E2)[3]. Acolbifene (EM-652) is devoid of intrinsic estrogenic activity and exhibits the strongest suppression of estradiol-stimulated cell proliferation in human breast cancer cells (ZR-75-1, MCF-7, T-47D)[4]. |
| ln Vivo |
Acolbifene (ACOL) decreases food consumption and dramatically lowers cholesterol in rats given a cholesterol-free diet[2]. Acolbifene (ACOL) decreases food consumption (16%) and weight gain (45%, mostly fat) in both dietary cohorts in a comparable way[2]. |
| Animal Protocol |
Female Sprague-Dawley rats (n = 42) initially weighing 175-200 g[2]. 2.5 mg/kg. Oral gavage, once daily for 21 d. |
| References |
[1].Recent advances in selective estrogen receptor modulators for breast cancer. Mini Rev Med Chem. 2009 Sep;9(10):1191-201. [2]. The selective estrogen receptor modulator acolbifene reduces cholesterolemia independently of its anorectic action in control and cholesterol-fed rats. J Nutr. 2005 Sep;135(9):2225-9. [3]. EM-800, a novel antiestrogen, acts as a pure antagonist of the transcriptional functions of estrogen receptors alpha and beta. Endocrinology. 1998 Jan;139(1):111-8. [4]. Synthesis and structure-activity relationships of analogs of EM-652 (acolbifene), a pure selective estrogen receptor modulator. Study of nitrogen substitution. J Enzyme Inhib Med Chem. 2005 Apr;20(2):165-77. [5]. EM-652 (SCH 57068), a third generation SERM acting as pure antiestrogen in the mammary gland and endometrium. J Steroid Biochem Mol Biol. Apr-Jun 1999;69(1-6):51-84. |
| Additional Infomation | Acolbifene is under investigation in clinical trial NCT01452373 (Dehydroepiandrosterone (DHEA) + Acolbifene Against Vasomotor Symptoms (Hot Flushes) in Postmenopausal Women). |
Solubility Data
| Solubility (In Vitro) | DMSO: ~50 mg/mL (~109.3 mM) |
| 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 | 2.1855 mL | 10.9275 mL | 21.8551 mL | |
| 5 mM | 0.4371 mL | 2.1855 mL | 4.3710 mL | |
| 10 mM | 0.2186 mL | 1.0928 mL | 2.1855 mL |