受注:045-509-1970 |
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C21H15F4N5O2S |
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分子量 | 477.43 | CAS No. | 956104-40-8 | ||||
Solubility (25°C)* | 体外 | DMSO | 95 mg/mL (198.98 mM) | ||||
Ethanol | 28 mg/mL (58.64 mM) | ||||||
Water | Insoluble | ||||||
体内 (毎回新しく調製した物を用意してください) |
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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. |
製品説明 | Apalutamide (ARN-509) is a selective and competitive androgen receptor inhibitor with IC50 of 16 nM in a cell-free assay, useful for prostate cancer treatment. Phase 3. |
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in vitro | ARN-509 (< 10 μM) inhibits androgen-mediated induction or repression of mRNA expression levels for 13 endogenous genes including PSA and TMPRSS2 in the LNCaP/AR prostate cancer cell line. ARN-509 (< 10 μM) inhibits the proliferative effect of R1881 (30 pM) in the LNCaP/AR prostate cancer cell line. ARN-509 (10 μM) impairs AR nuclear localization and thus reduces the concentration of AR available to bind androgen response elements (ARE) in LNCaP cells expressing AR-EYFP. ARN-509 (10 μM) is able to effectively compete with R1881 (1 nM) and prevent AR from binding to promoter regions. ARN-509 inhibits R1881-induced VP16-AR–mediated transcription with IC50 of 0.2 μM in Hep-G2 cells expressing a VP16-AR fusion protein and an ARE-driven luciferase reporter. [1] |
in vivo | ARN-509 (10 mg/kg/d, oral) inhibits tumor growth with decreased proliferative index and increased apoptotic rate in castrate male immunodeficient mice harboring LNCaP/AR-luc xenograft tumors. ARN-509 dose dependently inhibits tumor growth with highest efficacy at dose of 30 mg/kg/day in castrate male immunodeficient mice harboring LNCaP/AR-luc xenograft tumors. ARN-509 dosed at 10 mg/kg/d for 28 days results in a 3-fold reduction in prostates weight associated with lacking glandular secretory activity and 1.7-fold reduction in epididymis weight in adult male dogs. ARN-509 (10 mg/kg/d, oral) inhibits cell proliferation of prostate tissues in adult male dogs. [1] ARN-509 is safe and well tolerated in 24 patients with metastatic CRPC who has progressed on prior treatments and peak plasma concentrations occurred 2 to 3 hours after administration. ARN-509 results in durable PSA declines at doses ranging from 30 to 300 mg in patients with metastatic CRPC. [2] ARN-509 shows powerful anti-cancer activity and induces durable remissions long after therapy completion in castrate resistant prostate cancer mouse models. [3] |
細胞アッセイ | 細胞株 | LNCaP/AR prostate cancer cell line |
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濃度 | 10 μM | |
反応時間 | 48 hours | |
実験の流れ | Cells are incubated for 48 hours, after which ARN-509 is added in a 16 μL volume to the RPMI culture medium. For the antagonist mode assay, the ARN-509 is diluted in culture medium also containing 30 pM R1881. After 7 days' incubation, 16 μL of CellTiter-Glo Luminescent Cell Viability Assay is added and Relative Luminescence Units (RLUs) measured. | |
動物実験 | 動物モデル | Castrate male immunodeficient mice harboring LNCaP/AR-luc xenograft tumors |
投薬量 | 30 mg/kg/day | |
投与方法 | Orally |
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, , J Cancer, 2014, 5(2):133-42.
Data from [Data independently produced by , , Clin Cancer Res, 2017, 23(24):7608-7620]
Glucocorticoid treatment influences prostate cancer cell growth and the tumor microenvironment via altered glucocorticoid receptor signaling in prostate fibroblasts [ Oncogene, 2024, 43(4):235-247] | PubMed: 38017134 |
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 |
Androgen receptor blockade resistance with enzalutamide in prostate cancer results in immunosuppressive alterations in the tumor immune microenvironment [ J Immunother Cancer, 2023, 11(5)e006581] | PubMed: 37147019 |
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 |
Elevated FBXW10 drives hepatocellular carcinoma tumorigenesis via AR-VRK2 phosphorylation-dependent GAPDH ubiquitination in male transgenic mice [ Cell Rep, 2023, 42(7):112812] | PubMed: 37450367 |
PI5P4Kα supports prostate cancer metabolism and exposes a survival vulnerability during androgen receptor inhibition [ Sci Adv, 2023, 9(5):eade8641] | PubMed: 36724278 |
Understanding the role of Pax5 in development of taxane-resistant neuroendocrine like prostate cancers [ Res Sq, 2023, rs.3.rs-3464475] | PubMed: 38168280 |
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 |
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