生物活性

Onametostat (JNJ-64619178) is a pseudo-irreversible, orally active, and selective protein arginine methyltransferase 5 (PRMT5) inhibitor with an IC50 of 0.14 nM. Onametostat holds potential for research in lung cancer.

体外研究

JNJ-64619178 can bind to the SAM binding pocket, inhibiting the function of PRMT/MEP50 in a time-dependent manner. Various cell lines exhibit varying degrees of sensitivity to JNJ-64619178, indicating that the inhibition of PRMT5 by JNJ-64619178 primarily relies on genomic effects rather than general targeted cytotoxicity。

体内研究

Oral administration of 10 mg/kg JNJ-64619178 per day can selectively and effectively prevent the methylation of SMD1/3 proteins. SMD1/3 are key components of the spliceosome and substrates of PRMT5/MEP50. In a biomarker-driven human small cell lung cancer xenograft tumor model (NCI-H1048), JNJ-64619178 can induce tumor regression and prolong tumor growth inhibition after drug administration is terminated

激酶实验

细胞实验

动物实验

不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）

例如，已知某工具药用于小鼠的剂量为88 mg/kg , 则用于大鼠的剂量换算方法：将88 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到该药物用于大鼠的等效剂量44 mg/kg。

参考文献

https://www.researchgate.net/publication/318812366
2.Discovery of Novel PRMT5 Inhibitors by Virtual Screening and Biological Evaluations.2019;67(4):382-388.
3.Discovery and Pharmacological Characterization of JNJ-64619178, a Novel Small-Molecule Inhibitor of PRMT5 with Potent Antitumor Activity.2021 Dec;20(12):2317-2328.

体内溶解度

Clinical Trial Information ( data from http://clinicaltrials.gov )

注：以上所有数据均来自公开文献，并不保证对所有实验均有效，数据仅供参考。

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