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受注：045-509-1970 |
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化学情報
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Synonyms | TOK-001 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C26H32N2O |
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| 分子量 | 388.55 | CAS No. | 851983-85-2 | |
| Solubility (25°C)* | 体外 | Ethanol | 40 mg/mL warmed with 50ºC water bath (102.94 mM) | |
| DMSO | 24 mg/mL (61.76 mM) | |||
| Water | Insoluble | |||
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* <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. |
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溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | Galeterone (TOK-001) is a selective CYP17 inhibitor and androgen receptor (AR) antagonist with IC50 of 300 nM and 384 nM, respectively, and is a potent inhibitor of human prostate tumor growth. Phase 2. |
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| in vitro | Galeterone is effective at preventing binding of [3H]-R1881 to the mutant LNCaP AR (T877A) with IC50 of 845 nM. Galeterone inhibits the DHT-induced proliferation of LNCaP and LAPC4 cells in a dose-dependent manner with IC50 of 6 μM and 3.2 μM, respectively. [1] Galeterone also inhibits the binding of [3H]-R1881 to the T575A mutant AR in PC3 cells with IC50 of 454 nM. Galeterone potently inhibits the proliferation of LNCaP and LAPC4 cells in the absence of DHT stimulation with IC50 of 2.6 μM and 4 μM, respectively. Furthermore, Galeterone treatment increases the degradation rate of the AR in a dose-dependent manner. [2] Galeterone potently inhibits the growth of the androgen-independent cell lines PC-3 and DU-145 in a dose-dependent manner with GI50 of 7.82 μM and 7.55 μM, respectively. Galeterone induces the endoplasmic reticulum stress response resulting in down-regulation of cyclin D1 protein expression and cyclin E2 mRNA. [3] Galeterone effectively inhibits proliferation of HP-LNCaP and C4-2B cell lines with IC50 of 2.9 μM and 9.7 μM, respectively. Galeterone treatment at 1 μM effectively inhibits androgen receptor activation in LNCaP cells (50%) and HP-LNCaP cells (70%). Galeterone decreases activation of the androgen receptor in both LNCaP cells and HP-LNCaP cells with IC50 of 1 μM and 411 nM, respectively, and down-regulates androgen receptor protein expression by 50% after 24 hour of treatment. [4] Galeterone reduces AR protein and mRNA expression, antagonizes AR-dependent promoter activation induced by androgen, and significantly reduces the phospho-4EBP1 levels. [6] |
| in vivo | Administration of Galeterone at 50 mg/kg twice daily is very effective at inhibiting the growth of androgen-dependent LAPC4 human prostate tumor xenograft, with a 93.8% reduction in the mean final tumor volume compared with controls, and it is also significantly more effective than castration. [1] Treatment of Galeterone (0.13 mM/kg twice daily) or Galeterone (0.13 mmol/kg twice daily) plus castration induces regression of LAPC4 tumor xenografts in SCID mice by 26.55% and 60.67%, respectively. Treatments with Galeterone or Galeterone plus castration causes marked reduction in AR protein of 10- and 5-fold, respectively. [2] |
プロトコル(参考用のみ)
| キナーゼアッセイ | In vitro assay of CYP17 | |
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| The in vitro CYP17 inhibitory activity of Galeterone is evaluated using rapid acetic acid releasing assay (AARA), utilizing intact P450c17-expressing E. coli as the enzyme source. It involves the use of [21-3H]-17α-hydroxypregnenolone as the substrate, and CYP17 activity is measured by the amount of tritiated acetic acid formed during the cleavage of the C-21 side chain of the substrate. IC50 value is obtained directly from plots relating percentage inhibition versus inhibitor concentration over appropriate ranges. | ||
| 細胞アッセイ | 細胞株 | LNCaP and LAPC4 |
| 濃度 | Dissolved in DMSO, final concentrations ~20 μM | |
| 反応時間 | 7 days | |
| 実験の流れ | Cells are seeded in 24 well multi-well plates. Cells are treated with the increasing concentration of Galeterone in steroid free medium with or without 1 nM DHT (LNCaP), or 10 nM DHT (LAPC4) and allowed to grow for 7 days. The number of viable cells is compared by MTT assay (LAPC4) or XTT assay (LNCaP) on the 7th day. |
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| 動物実験 | 動物モデル | Male severe combined immunodeficient (SCID) mice inoculated subcutaneously (s.c.) with LAPC4 cells |
| 投薬量 | 50 mg/kg | |
| 投与方法 | Injection s.c. twice daily | |
参考
カスタマーフィードバック
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, , Biochem Biophys Res Commun, 2016, 477(4):1005-10.
Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：
| Desorption Electrospray Ionization Mass Spectrometry Assay for Label-Free Characterization of SULT2B1b Enzyme Kinetics [ ChemMedChem, 2022, e202200043] | PubMed: 35080134 |
| Galeterone sensitizes breast cancer to chemotherapy via targeting MNK/eIF4E and β-catenin [ Cancer Chemother Pharmacol, 2020, 10.1007/s00280-020-04195-w] | PubMed: 33159561 |
| New steroidal oxazolines, benzoxazoles and benzimidazoles related to abiraterone and galeterone. [ Steroids, 2020, 153:108534] | PubMed: 31678134 |
| Comparison of [17(20)E]-21-Norpregnene oxazolinyl and benzoxazolyl derivatives as inhibitors of CYP17A1 activity and prostate carcinoma cells growth [ Steroids, 2018, 129:24-34] | PubMed: 29183745 |
| Conjugates of 17-substituted testosterone and epitestosterone with pyropheophorbide a differing in the length of linkers [Zolottsev VA, et al. Steroids, 2018, 138:82-90] | PubMed: 30033342 |
| Specificity of anti-prostate cancer CYP17A1 inhibitors on androgen biosynthesis [Udhane SS, et al. Biochem Biophys Res Commun, 2016, 477(4):1005-10] | PubMed: 27395338 |
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。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。