受注:045-509-1970 |
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Synonyms | BAY-1841788 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C19H19ClN6O2 |
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分子量 | 398.85 | CAS No. | 1297538-32-9 | |
Solubility (25°C)* | 体外 | DMSO | 80 mg/mL (200.57 mM) | |
Ethanol | 4 mg/mL warmed with 50ºC water bath (10.02 mM) | |||
Water | 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 | Darolutamide (ODM-201, BAY-1841788) is a novel androgen receptor (AR) antagonist that blocks AR nuclear translocation with Ki of 11 nM. Phase 3. |
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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] |
キナーゼアッセイ | AR binding affinity | |
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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. |
Data from [Data independently produced by , , Clin Cancer Res, 2018, doi:10.1158/1078-0432.CCR-18-1469]
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。
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