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Synonyms | TSE-424 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C30H34N2O3.HCl |
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分子量 | 507.06 | CAS No. | 198480-56-7 | |
Solubility (25°C)* | 体外 | DMSO | 90 mg/mL (177.49 mM) | |
Water | Insoluble | |||
Ethanol | Insoluble | |||
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
製品説明 | Bazedoxifene HCl (WAY-140424, TSE-424) is a novel, non-steroidal, indole-based estrogen receptor modulator (SERM) binding to both ERα and ERβ with IC50 of 23 nM and 89 nM, respectively. |
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in vitro | Bazedoxifene is a third generation selective estrogen receptor modulator (SERM). Bazedoxifene does not stimulate ERα mediated transcriptional activity and acts as an antagonist to estradiol in cultured breast cancer (bMCF-7) cells. Similar results are seen in other cell lines including CHO (ovarian), HepG2 (hepatic) or GTI-7 (neuronal) with bazedoxifene having no ERα agonist activity and acting as an antagonist to estradiol action.[2] Bazedoxifene does not stimulate proliferation of MCF-7 cells but did inhibit 17β-estradiol-induced proliferation with IC50 of 0.19 nM. [3] |
in vivo | In an immature rat model, bazedoxifene increases uterine wet weight 35% at a dose of 0.5 mg/kg compared to an 85% increase with raloxifene at the same dose and a 300% increase in uterine weight with ethinyl estradiol at a dose of 10 μg/kg. Ovarectomized rats treated with 0.3 mg/d bazedoxifene displayed maintenance of bone mass and bone strength similar to effects seen with 2 μg/d ethinyl estradiol, 3 mg/d raloxifene, or sham operated animals. [2] |
キナーゼアッセイ | Ligand binding competition experiments | |
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Test compounds are initially solubilized in DMSO and the final concentration of DMSO in the binding assay is ≤ 1%. Eight dilutions of each test compound are used as an unlabelled competitor for [3H]17β-estradiol. Typically, a set of compound dilutions would be tested simultaneously on human, rat and mouse ER-α and ER-β. The results are plotted as measured DPM vs. concentration of test compound. For dose-response curve fitting, a four parameter logistic model on the transformed, weighted data are fit and the IC50 is defined as the concentration of compound decreasing maximum [3H]estradiol binding by 50%. For active compounds, the IC50 is determined at least three times. It should be noted that IC50 values are not direct measures of a ligand’s affinity for the receptor. Rather, they can only be compared as relative values, in this case to 17β-estradiol. | ||
細胞アッセイ | 細胞株 | MCF-7 |
濃度 | ~10 nM | |
反応時間 | 7 days | |
実験の流れ | For the proliferation assay, cells are plated at 20,000 cells/well in a 24-well plate in DMEM/F12 (50:50) (phenol red-free) with 10% charcoal/dextran-treated FBS and 1 × GlutaMAX-1. After overnight incubation, the medium is aspirated and treatments in DMEM/F12 (50:50) (phenol red-free) with 2% charcoal/dextran-treated FBS and 1 × GlutaMAX-1 are added to the wells. Each plate has a vehicle (baseline proliferation) and treatments. Treatments included 10 pM 17β-estradiol determined to be the EC80 for 17β-estradiol and 17β-estradiol in combination with six concentrations of BZA. Treatments from d 1 are renewed on d 3 and d 6 by aspirating medium from wells and replacing with fresh medium and treatments. On d 7, cells are detached from the plate using trypsin-EDTA and counted using a Multisizer II. | |
動物実験 | 動物モデル | Sprague Dawley rats |
投薬量 | 0.5 and 5.0 mg/kg | |
投与方法 | SC |
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Data from [J Med Chem, 2014, 57(3), 632-41]
Data from [Data independently produced by , , PLoS One, 2016, 24;11(3):e0151182]
The Interleukin-11/IL-11 Receptor Promotes Glioblastoma Survival and Invasion under Glucose-Starved Conditions through Enhanced Glutaminolysis [ Int J Mol Sci, 2023, 24(4)3356] | PubMed: 36834778 |
Targeting the gp130/STAT3 Axis Attenuates Tumor Microenvironment Mediated Chemoresistance in Group 3 Medulloblastoma Cells [ Cells, 2022, 11(3)381] | PubMed: 35159191 |
Utilizing an Endogenous Progesterone Receptor Reporter Gene for Drug Screening and Mechanistic Study in Endometrial Cancer [ Cancers (Basel), 2022, 14(19)4883] | PubMed: 36230806 |
A compendium of kinetic modulatory profiles identifies ferroptosis regulators [ Nat Chem Biol, 2021, 10.1038/s41589-021-00751-4] | PubMed: 33686292 |
Synergistic PIM kinase and proteasome inhibition as a therapeutic strategy for MYC-overexpressing triple-negative breast cancer [ Cell Chem Biol, 2021, S2451-9456(21)00400-1] | PubMed: 34525344 |
Bazedoxifene inhibits sustained STAT3 activation and increases survival in GBM [ Transl Oncol, 2021, 14(11):101192] | PubMed: 34365219 |
Autocrine and paracrine signaling contributes to acquired chemotherapeutic resistance in Group 3 medulloblastoma [ B.S., The University of Arizona, 2021, ] | PubMed: none |
The dysregulated pharmacology of clinically relevant ESR1 mutants is normalized by ligand-activated WT receptor. [ Mol Cancer Ther, 2020, 7 pii: molcanther] | PubMed: 32381587 |
G1T48, an oral selective estrogen receptor degrader, and the CDK4/6 inhibitor lerociclib inhibit tumor growth in animal models of endocrine-resistant breast cancer. [ Breast Cancer Res Treat, 2020, 10.1007/s10549-020-05575-9] | PubMed: 32130619 |
Repurposing the Selective Estrogen Receptor Modulator bazedoxifene to Suppress Gastrointestinal Cancer Growth [ EMBO Mol Med, 2019, 11(4):e9539] | PubMed: 30885958 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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