Onametostat (JNJ-64619178)

製品コードS8624 バッチS862403

印刷

化学情報

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

97 mg/mL (200.67 mM)

Water

˂1 mg/mL

Ethanol

˂1 mg/mL

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 Corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	5.000mg/ml (10.34mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. 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	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	Onametostat (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 this compound 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	Onametostat (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. It 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 this compound has been identified, with the observed toxicity consistent with on-target activity. In summary, it has a favorable preclinical package that supports clinical testing in patients diagnosed with lung cancer and hematologic malignancies^[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.

参考

https://www.researchgate.net/publication/318812366
https://pubmed.ncbi.nlm.nih.gov/30930442/
https://pubmed.ncbi.nlm.nih.gov/34583982/

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：

Heterogeneity-driven phenotypic plasticity and treatment response in branched-organoid models of pancreatic ductal adenocarcinoma [ Nat Biomed Eng, 2024, 10.1038/s41551-024-01273-9]	PubMed: 39658630
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
Development and validation of a generic methyltransferase enzymatic assay based on an SAH riboswitch [ SLAS Discov, 2024, 29(4):100161]	PubMed: 38788976
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。