Darolutamide (ODM-201)

製品コードS7559 バッチS755902

印刷

化学情報

Chemical Structure Synonyms BAY-1841788 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C19H19ClN6O2
分子量 398.85 CAS No. 1297538-32-9
Solubility (25°C)* 体外 DMSO 80 mg/mL (200.57 mM)
Ethanol (warmed with 50ºC water bath) 40 mg/mL (100.28 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
4.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 80 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Darolutamide (ODM-201, BAY-1841788) is a novel androgen receptor (AR) antagonist that blocks AR nuclear translocation with Ki of 11 nM. Phase 3.
in vitro In AR-HEK293 cells stably expressing full-length hAR, ODM-201 inhibits human AR (hAR) with IC50 of 26 nM. ODM-201 inhibits VCaP cell proliferation with IC50 of 230 nM, while has no effect on the viability of AR-negative cell lines tested, DU-145 prostate cancer cells and H1581 lung cancer cells. [1]
in vivo In mice bearing VCaP xenografts, ODM-201 (50 mg/kg, p.o.) significantly inhibits castration-resistant prostate tumor growth. [1]

プロトコル(参考用のみ)

キナーゼアッセイ AR binding affinity
AR binding affinities of test compounds are studied in cytosolic lysates obtained from ventral prostates of castrated rats by a competition binding assay. Fresh prostates are minced and homogenized with Buffer A containing protease inhibitors. The homogenates are centrifuged and the resultant supernatants are treated with a dextran-coated charcoal solution to remove endogenous steroids. The dissociation constant of the radio ligand [3H]mibolerone for isolated rat ARs is determined in a saturation binding experiment. For the determination of Ki values, prostate cytosol preparations and 1 nM [3H]mibolerone are incubated with increasing concentrations of test compounds overnight. After the incubation, bound and free steroids are separated by treatment with 100 μL of dextran-coated charcoal suspension. Bound radioactivity is determined by counting 100 μL of supernatant fraction in 200 μL of scintillation fluid using a microbeta counter. All procedures are carried out at 0–4 °C.
細胞アッセイ 細胞株 DU-145, H1581, and VCaP cells
濃度 ~10 μM
反応時間 4 days
実験の流れ VCaP cells are treated with a submaximal concentration of mibolerone (0.1 nM) and increasing concentrations of test compounds in steroid-free assay medium supplemented with 4 mM GlutaMAX. After a 4-day incubation with the compounds, cell viability is measured using a WST-1 cell proliferation assay. To rule out non-AR –mediated toxicity, AR-negative PC cells (DU-145) and lung cancer cells (H1581) are treated with an increasing concentration of ODM-201, and cell viability is measured as described above.
動物実験 動物モデル BALB/c nude male mice bearing VCaP xenografts
投薬量 50 mg/kg, bid
投与方法 p.o.

カスタマーフィードバック

Data from [Data independently produced by , , Clin Cancer Res, 2018, doi:10.1158/1078-0432.CCR-18-1469]

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：

Loss of LCMT1 and biased protein phosphatase 2A heterotrimerization drive prostate cancer progression and therapy resistance [ Nat Commun, 2023, 14(1):5253] PubMed: 37644036
Loss of LCMT1 and biased protein phosphatase 2A heterotrimerization drive prostate cancer progression and therapy resistance [ Nat Commun, 2023, 14(1):5253] PubMed: 37644036
Pharmacological Targeting of Androgen Receptor Elicits Context-Specific Effects in Estrogen Receptor-Positive Breast Cancer [ Cancer Res, 2023, 83(3):456-470] PubMed: 36469363
Allosteric inhibition of HSP70 in collaboration with STUB1 augments enzalutamide efficacy in antiandrogen resistant prostate tumor and patient-derived models [ Pharmacol Res, 2023, 189:106692] PubMed: 36773708
Ferroptosis heterogeneity in triple-negative breast cancer reveals an innovative immunotherapy combination strategy [ Cell Metab, 2022, S1550-4131-2200411-9] PubMed: 36257316
A novel inhibitor of ARfl and ARv7 induces protein degradation to overcome enzalutamide resistance in advanced prostate cancer [ Acta Pharm Sin B, 2022, 12(11):4165-4179] PubMed: 36386477
An oral first-in-class small molecule RSK inhibitor suppresses AR variants and tumor growth in prostate cancer [ Cancer Sci, 2022, 113(5):1731-1738] PubMed: 35118769
Impact of Androgen Receptor Activity on Prostate-Specific Membrane Antigen Expression in Prostate Cancer Cells [ Int J Mol Sci, 2022, 23(3)1046] PubMed: 35162969
Targeting transcriptional regulation of SARS-CoV-2 entry factors ACE2 and TMPRSS2 [ Proc Natl Acad Sci U S A, 2020, 202021450] PubMed: 33310900
Effects of MTX-23, a Novel PROTAC of Androgen Receptor Splice Variant-7 and Androgen Receptor, on CRPC resistant to Second-Line Antiandrogen Therapy [ Mol Cancer Ther, 2020, molcanther.0417.2020] PubMed: 33277442

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。