Bazedoxifene HCl
(Synonyms: 盐酸巴多昔芬,TSE-424 hydrochloride) 目录号 : GC10245
Bazedoxifene HCl (TSE-424 hydrochloride) 是一种具有口服活性、可渗透 BBB 的非甾体选择性雌激素受体调节剂 (SERM)，对 ERα 的 IC50 分别为 23 nM 和 99 nM；和ERβ，分别。盐酸巴多昔芬可用于骨质疏松症的研究。 Bazedoxifene HCl 作为 IL-6/GP130 蛋白质-蛋白质相互作用的抑制剂。 Bazedoxifene HCl 可用于胰腺癌的研究。
Cas No.:198480-56-7
Sample solution is provided at 25 µL, 10mM.
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Bazedoxifene HCl is a novel, non-steroidal and indole-based estrogen receptor modulator (SERM). The IC50 value of bazedoxifene against ERα and ERβ is 23 nM and 89 nM, respectively [1,2].
The estrogen receptor (ER) contains two subtypes, ERα and ERβ. ERs are widely expressed in different tissue types such as kidney, brain, bone, heart, prostate, and endothelial cells. Estrogen and the ERs have been involved in most cancers such as breast cancer,ovarian cancer,colon cancer,prostate cancer, and endometrial cancer [3].
In vitro: Bazedoxifene is a selective SERM currently in development for osteoporosis prevention and treatment. Bazedoxifene was the third generation SERM. In cultured breast cancer (bMCF-7) cells, bazedoxifenedidn’t stimulate ERα mediated transcriptional activity and acted as an antagonist to estradiol. Similar results were also 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 didn’t stimulate proliferation of MCF-7 cells but inhibited 17β-estradiol-induced proliferation with an IC50 value of 0.19 nM [4].
In vivo:In an immature rat model, bazedoxifene increased 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. In an immature rat uterine model, bazedoxifene (0.5 and 5.0 mg/kg) was associated with less increase in uterine wet weight than either ethinyl estradiol (10 μg/kg) or raloxifene (0.5 and 5.0 mg/kg) [4].
References:
[1]. Miller C P, Collini M D, Tran B D, et al. Design, synthesis, and preclinical characterization of novel, highly selective indole estrogens[J]. Journal of medicinal chemistry, 2001, 44(11): 1654-1657.
[2]. Biskobing D M. Update on bazedoxifene: A novel selective estrogen receptor modulator[J]. Clinical interventions in aging, 2007, 2(3): 299.
[3]. Harris H A, Albert L M, Leathurby Y, et al. Evaluation of an estrogen receptor-β agonist in animal models of human disease[J]. Endocrinology, 2003, 144(10): 4241-4249.
[4]. Komm B S, Kharode Y P, Bodine P V N, et al. Bazedoxifene acetate: a selective estrogen receptor modulator with improved selectivity[J]. Endocrinology, 2005, 146(9): 3999-4008.
| Cell experiment [1]: | |
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Cell lines |
CHO cells, HepG2 cells, GT1–7 cells, MCF-7 cells |
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Preparation method |
The solubility of this compound in DMSO is >25.4mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
0.1 pM-10 nM |
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Applications |
Co-treatment with 1.0 nM 17β-estradiol and bazedoxifene had an IC50 of 22.0 nM in CHO cells, 4.97 nM in HepG2 cells, and 10.0 nM in GT1–7 cells. In HepG2 cells transfected with hepatic lipase promoter luciferase construct, bazedoxifene functioned as an agonist with an EC50 of 100.0 nM. In MCF-7 cell, co-treatment with 17β-estradiol and bazedoxifene dose-dependently inhibited cell proliferation with an IC50 of 0.19 nM. |
| Animal experiment [1]: | |
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Animal models |
An immature rat uterine model |
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Dosage form |
0.5 and 5.0 mg/kg; once daily for 3 d; administered orally |
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Application |
In an immature rat uterine model, bazedoxifene (BZA) increased uterine wet weight by 35% at 0.5 mg/kg andno significant difference at 5 mg/kg. Histological examination of the entire uterus revealed BZA does not affect luminal epithelial cell hypertrophy or hyperplasia, myometrial hypertrophy, or luminal distention. BZA resulted in only a slight, insignificant increase in luminal cell height. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Komm B S, Kharode Y P, Bodine P V N, et al. Bazedoxifene acetate: a selective estrogen receptor modulator with improved selectivity[J]. Endocrinology, 2005, 146(9): 3999-4008. | |
| Cas No. | 198480-56-7 | SDF | |
| 别名 | 盐酸巴多昔芬,TSE-424 hydrochloride | ||
| 化学名 | 1-[[4-[2-(azepan-1-yl)ethoxy]phenyl]methyl]-2-(4-hydroxyphenyl)-3-methylindol-5-ol;hydrochloride | ||
| Canonical SMILES | CC1=C(N(C2=C1C=C(C=C2)O)CC3=CC=C(C=C3)OCCN4CCCCCC4)C5=CC=C(C=C5)O.Cl | ||
| 分子式 | C30H34N2O3.HCl | 分子量 | 507.06 |
| 溶解度 | ≥ 25.35mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.9722 mL | 9.8608 mL | 19.7215 mL |
| 5 mM | 0.3944 mL | 1.9722 mL | 3.9443 mL |
| 10 mM | 0.1972 mL | 0.9861 mL | 1.9722 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet