Onametostat (JNJ-64619178)

製品コードS8624 バッチS862401

印刷

化学情報

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

C22H23BrN6O2
分子量 483.36 CAS No. 2086772-26-9
Solubility (25°C)* 体外 DMSO 100 mg/mL (206.88 mM)
 
 
* <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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生物活性

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.
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].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 Cell-free assays
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.

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：

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。

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