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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 | C22H23BrN6O2 |
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分子量 | 483.36 | CAS No. | 2086772-26-9 | |
Solubility (25°C)* | 体外 | DMSO | 97 mg/mL (200.67 mM) | |
Water | Insoluble | |||
Ethanol | 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 | Onametostat (JNJ-64619178) is a PRMT5 inhibitor with high selectivity and potency (subnanomolar range, PRMT5-MEP-50 IC50=0.14 nM) under different in vitro and cellular conditions, paired with favorable pharmacokinetics and safety properties. |
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in vitro | JNJ-64619178 binds into the SAM binding pocket and reaches the substrate binding pocket to inhibit PRMT5/MEP50 function in a time-dependent manner. Broad cell line panel profiling of JNJ-64619178 reveals a wide range of sensitivity, which is indicative of a genomic dependency instead of a general cytotoxic on-target consequence of PRMT5 inhibition[1]. |
in vivo | JNJ-64619178, dosed orally (10 mg/kg, every day), shows selective and efficient blockage of the methylation of SMD1/3 proteins, which are crucial components of the spliceosome and substrates of PRMT5/MEP50. JNJ-64619178 also demonstrates tumor regression in a biomarker-driven human small cell lung cancer xenograft model (NCI-H1048) and prolongs tumor growth inhibition after dosing cessation. In rodent and nonrodent toxicology studies, a tolerated dose of JNJ-64619178 has been identified, with the observed toxicity consistent with on-target activity. In summary, JNJ-64619178 has a favorable preclinical package that supports clinical testing in patients diagnosed with lung cancer and hematologic malignancies1[1]. |
細胞アッセイ | 細胞株 | Cell-free assays |
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濃度 | 0.14 nM (IC50) | |
反応時間 | ||
実験の流れ | ||
動物実験 | 動物モデル | C57BL/6 mice |
投薬量 | 10 mg/kg | |
投与方法 | p.o. |
Inhibition of epigenetic and cell cycle-related targets in glioblastoma cell lines reveals that onametostat reduces proliferation and viability in both normoxic and hypoxic conditions [ Sci Rep, 2024, 14(1):4303] | PubMed: 38383756 |
Long non-coding RNA-derived peptides are immunogenic and drive a potent anti-tumour response [ Nat Commun, 2023, 14(1):1078] | PubMed: 36841868 |
PRMT5 reduces immunotherapy efficacy in triple-negative breast cancer by methylating KEAP1 and inhibiting ferroptosis [ J Immunother Cancer, 2023, 11(6)e006890] | PubMed: 37380368 |
Epigenetic drug screening defines a PRMT5 inhibitor-sensitive pancreatic cancer subtype [ JCI Insight, 2022, 7(10)e151353] | PubMed: 35439169 |
Tadalafil increases the antitumor activity of 5-FU through inhibiting PRMT5-mediated glycolysis and cell proliferation in colorectal cancer [ Cancer Metab, 2022, 10(1):22] | PubMed: 36474242 |
Acquired resistance to PRMT5 inhibition induces concomitant collateral sensitivity to paclitaxel [ Proc Natl Acad Sci U S A, 2021, 118(34)e2024055118] | PubMed: 34408017 |
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。