Onametostat

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Chemical Structure| 2086772-26-9 同义名 : JNJ-64619178
CAS号 : 2086772-26-9
货号 : A1176455
分子式 : C22H23BrN6O2
纯度 : 99%+
分子量 : 483.36
MDL号 : MFCD31813596
存储条件：

Pure form Keep in dark place, inert atmosphere, 2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 120 mg/mL(248.26 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 Protein arginine methyltransferase 5 (PRMT5) is responsible for the mono-methylation and symmetric dimethylation of arginine, and its expression level and methyl transferring activity have been demonstrated to have a close relationship with tumorigenesis, development and poor clinical outcomes of human cancers[1].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. 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[2].JNJ-64619178 demonstrated a prolonged inhibition of PRMT5 and potent antiproliferative activity in subsets of cancer cell lines derived from various histologies, including lung, breast, pancreatic, and hematological malignancies[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.07mL

0.41mL

0.21mL

10.34mL

2.07mL

1.03mL

20.69mL

4.14mL

2.07mL
参考文献

[1] Kongkai Zhu, Jingwei Shao,et al. Rational Design, synthesis and biological evaluation of novel triazole derivatives as potent and selective PRMT5 inhibitors with antitumor activity. J Comput Aided Mol Des.2019 Aug;33(8):775-785.

[2] Dirk Brehmer,et al. Abstract DDT02-04: A novel PRMT5 inhibitor with potent in vitro and in vivo activity in preclinical lung cancer models.

[3]Dirk Brehmer, Lijs Beke,et al. Discovery and Pharmacological Characterization of JNJ-64619178, a Novel Small-Molecule Inhibitor of PRMT5 with Potent Antitumor Activity. Mol Cancer Ther. 2021 Dec;20(12):2317-2328.