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Droloxifene (3-Hydroxytamoxifen) is an oral bioactive selective estrogen receptor modulator (SERM) that functions as an ER antagonist in breast tissue and an ER agonist in bone. It is an analogue of tamoxifen. It inhibits bone resorption and turnover, raises luteal cell apoptosis, has antiestrogenic and anti-implantation properties, and lowers E-selectin levels.
Physicochemical Properties
| Molecular Formula | C26H29NO2 |
| Molecular Weight | 387.51396 |
| Exact Mass | 579.247 |
| Elemental Analysis | C, 80.59; H, 7.54; N, 3.61; O, 8.26 |
| CAS # | 82413-20-5 |
| Related CAS # | 97752-20-0 (citrate);82413-20-5; |
| PubChem CID | 3033767 |
| Appearance | White to off-white solid powder |
| Density | 1.092 g/cm3 |
| Boiling Point | 526.6ºC at 760 mmHg |
| Melting Point | 127-129ºC |
| Index of Refraction | 1.596 |
| LogP | 4.453 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 3 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 29 |
| Complexity | 501 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | C(/C1C=CC=C(O)C=1)(\C1C=CC(OCCN(C)C)=CC=1)=C(\C1C=CC=CC=1)/CC |
| InChi Key | ZQZFYGIXNQKOAV-OCEACIFDSA-N |
| InChi Code | InChI=1S/C26H29NO2/c1-4-25(20-9-6-5-7-10-20)26(22-11-8-12-23(28)19-22)21-13-15-24(16-14-21)29-18-17-27(2)3/h5-16,19,28H,4,17-18H2,1-3H3/b26-25+ |
| Chemical Name | 3-[(E)-1-[4-[2-(dimethylamino)ethoxy]phenyl]-2-phenylbut-1-enyl]phenol |
| Synonyms | Droloxifene; K 060E; K060E; K-060E; K 21060E; K 21060E |
| 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 | Droloxifene (10 nM; 16-18 hours) induces apoptosis in MCF-7 cells[1]. |
| ln Vivo | Droloxifene (5-20 mg/kg; p.o.; daily for 4 weeks) enhances the BMD of DFM at 10 mg/kg and totally stops the BMC and BMD of DFM from declining when ovariectomized (OVX) is administered at 20 mg/kg/day[3]. |
| Animal Protocol |
5-month-old sham-operate rats[3] 5, 10, 20 mg/kg Oral; daily for 4 weeks |
| ADME/Pharmacokinetics |
Metabolism / Metabolites 3-Hydroxytamoxifen has known human metabolites that include N-Demethyldroloxifene and (2S,3S,4S,5R)-6-[3-[(E)-1-[4-[2-(dimethylamino)ethoxy]phenyl]-2-phenylbut-1-enyl]phenoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid. 3-Hydroxytamoxifen is a known human metabolite of tamoxifen. |
| References |
[1]. Cardiovascular effects of droloxifene, a new selective estrogen receptor modulator, in healthypostmenopausal women. Arterioscler Thromb Vasc Biol. 2000 Jun;20(6):1606-12. [2]. Common mechanism for the estrogen agonist and antagonist activities of droloxifene. J Cell Biochem. 1997 May;65(2):159-71. [3]. Droloxifene, a new estrogen antagonist/agonist, prevents bone loss in ovariectomized rats. ndocrinology. 1995 Jun;136(6):2435-41. [4]. Anti-implantation effect of droloxifene in rats and its relationship with anti-estrogenic activity. Acta Pharmacol Sin. 2005 Oct;26(10):1243-7. |
| Additional Infomation |
Droloxifene is a stilbenoid. Droloxifene, a derivative of the triphenylethylene drug tamoxifen, is a novel selective estrogen receptor modulator (SERM). Droloxifene also exhibits more rapid pharmacokinetics, reaching peak concentrations and being eliminated much more rapidly than tamoxifen. Its higher affinity to the estrogen receptor, higher anti-estrogenic to estrogenic ratio, more effective inhibition of cell growth and division in estrogen receptor-positive cell lines, and lower toxicity give it theoretical advantages over tamoxifen in the treatment of human breast cancer. Short-term toxicity was generally mild, and similar to that seen with other antiestrogens. Droloxifene appears active and tolerable. It may have a particular role in situations in which rapid pharmacokinetics, or an increased antiestrogenic to estrogenic ratio, are required. Droloxifene may also be a potentially useful agent for the treatment of postmenopausal osteoporosis because it can prevent estrogen deficiency-induced bone loss without causing uterine hypertrophy. Droloxifene may have an effect on bone and breast tissue because it induces apoptosis. Droloxifene has an anti-implantation effect in rats, and the effect appears to be not completely due to its anti-estrogenic activity. Droloxifene is a phenolic analogue of tamoxifen, a nonsteroidal selective estrogen receptor modulator (SERM). Droloxifene competitively inhibits the binding of estradiol to estrogen receptors, thereby preventing the receptor from binding to the estrogen-response element on DNA. The result is a reduction in DNA synthesis and cellular response to estrogen. (NCI) |
Solubility Data
| Solubility (In Vitro) | DMSO: ~50 mg/mL (~129.0 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (12.90 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5806 mL | 12.9029 mL | 25.8058 mL | |
| 5 mM | 0.5161 mL | 2.5806 mL | 5.1612 mL | |
| 10 mM | 0.2581 mL | 1.2903 mL | 2.5806 mL |