Erteberel (also known as LY500307) is a novel, potent and selective estrogen receptor beta (ERβ) inhibitor with Ki and EC50 of 1.54 nM and 3.61 nM, respectively. It has anti-tumor activities and was developed for the treatment of benign prostatic hyperplasia. LY500307 was well tolerated in BPH patients with LUTS at doses up to 25 mg once daily for 24 weeks. The study was terminated early because of inadequate efficacy.
Physicochemical Properties
| Molecular Formula | C18H18O3 |
| Molecular Weight | 282.333725452423 |
| Exact Mass | 282.125 |
| CAS # | 533884-09-2 |
| PubChem CID | 10286159 |
| Appearance | Off-white to light brown solid powder |
| Density | 1.268 |
| Boiling Point | 485.2±45.0 °C at 760 mmHg |
| Flash Point | 247.3±28.7 °C |
| Vapour Pressure | 0.0±1.3 mmHg at 25°C |
| Index of Refraction | 1.639 |
| LogP | 3.84 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 3 |
| Rotatable Bond Count | 1 |
| Heavy Atom Count | 21 |
| Complexity | 364 |
| Defined Atom Stereocenter Count | 3 |
| SMILES | C1C[C@H]2[C@@H](C1)C3=C(C=CC(=C3)O)O[C@H]2C4=CC=C(C=C4)O |
| InChi Key | XIESSJVMWNJCGZ-VKJFTORMSA-N |
| InChi Code | InChI=1S/C18H18O3/c19-12-6-4-11(5-7-12)18-15-3-1-2-14(15)16-10-13(20)8-9-17(16)21-18/h4-10,14-15,18-20H,1-3H2/t14-,15+,18+/m1/s1 |
| Chemical Name | (3aS,4R,9bR)-4-(4-hydroxyphenyl)-1,2,3,3a,4,9b-hexahydrocyclopenta[c]chromen-8-ol |
| Synonyms | LY500307; LY-500307; LY 500307 |
| 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
| ln Vitro | In vitro, Erteberel treatment (0.25-10 μM, 72 hours) significantly inhibited GBM cell proliferation but had no effect on normal astrocytes [2]. Erteberel induces apoptosis in GBM cells. Erteberel affects several processes linked to the cell cycle, DNA damage response, and apoptosis [2]. Erteberel (0-1000 μM) sensitizes GBM cells to a number of chemotherapeutic medications that are licensed by the FDA, such as temozolomide, lomustine, and cisplatin [2]. |
| ln Vivo | Erteberel treatment (5 mg/Kg body weight/day, oral, for 28 days) significantly slowed tumor growth and increased GBM tumor cell apoptosis in an orthotopic model [2]. In the GL26 syngeneic glioma model, ERTEBEL (5 mg/Kg body weight/day, oral, 40–50 days) treatment increases the overall survival of tumor-bearing mice [2]. |
| Cell Assay |
Cell Viability Assay[2] Cell Types: U87, U251, T98G and normal astrocytes Tested Concentrations: 0.25, 0.5, 1, 2, 4, 6, 8 and 10 μM Incubation Duration: 72 hrs (hours) Experimental Results: Erteberel treatment Dramatically diminished viability was studied in various GBM cell lines in a dose-dependent manner. In contrast, the viability of normal astrocytes was not affected at the tested doses, indicating that Erteberel has tumor cell-specific activity [2]. |
| Animal Protocol |
Animal/Disease Models: Athymic mice (5-7 weeks) vaccinated with OVCAR-3 cells [2] Doses: 5 mg/kg body weight Route of Administration: Orally, one time/day for 28 days Experimental Results: Immunohistochemical analysis demonstrated that Erteberel Treatment Dramatically diminished the number of proliferation marker Ki-67-positive cells and increased the number of TUNEL-positive apoptotic cells [2]. |
| References |
[1]. Pharmacological activation of estrogen receptor beta augments innate immunity to suppress cancer metastasis. Proc Natl Acad Sci U S A. 2018 Apr 17;115(16):E3673-E3681. [2]. Selective Estrogen Receptor β Agonist LY500307 as a Novel Therapeutic Agent for Glioblastoma. Sci Rep. 2016 Apr 29;6:24185. |
| Additional Infomation | Erteberel is an estrogen receptor beta agonist that has been used in trials studying the treatment of Benign Prostatic Hyperplasia. |
Solubility Data
| Solubility (In Vitro) | DMSO : ≥ 30 mg/mL (~106.26 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 | 3.5420 mL | 17.7098 mL | 35.4195 mL | |
| 5 mM | 0.7084 mL | 3.5420 mL | 7.0839 mL | |
| 10 mM | 0.3542 mL | 1.7710 mL | 3.5420 mL |