同义名 :	-
	CAS号 :	2080306-20-1
	货号 :	A896158
	分子式 :	C28H34N4O2
	纯度 :	99%+
	分子量 :	458.6
	MDL号 :	MFCD30720896
	存储条件：	Pure form Keep in dark place, sealed in dry, 2-8°C In solvent -20°C:3-6个月-80°C:12个月
	溶解度 :	-
	动物实验配方：

生物活性

描述

Protein arginine methyltransferase 4 (PRMT4) is a transcription regulator involved in the modulation of oxidative stress and autophagy[1].TP-064 is a potent and selective PRMT4 inhibitor. The in vitro activity of TP-064 includes inhibition of PRMT4 with IC50 < 10nM for methylation of H3 (1-25) and greater than 100-fold selectivity over other histone methyltransferases and non-epigenetic targets. In cellular assays, TP-064 inhibits the methylation of MED12 with IC50 = 43 nM.TP-064 induced a dose-dependent decrease in lipopolysaccharide-induced ex vivo blood monocyte Tnfα secretion (p < 0.05 for trend) in the context of unchanged blood monocyte concentrations and neutrophilia induction (p < 0.01 for trend). A dose-dependent decrease in gonadal white adipose tissue expression levels of PPARγ target genes was detected, which translated into a reduced body weight gain after high dose TP-064 treatment (p < 0.05). TP-064 treatment also dose-dependently downregulated gene expression of the glycogen metabolism related protein G6pc in the liver (p < 0.001 for trend)[2].TP-064 treatment downregulated hepatic mRNA expression levels of the PRMT4 target genes glucose-6-phosphatase catalytic subunit (-50%, P < 0.05) and the cyclin-dependent kinases 2 (-50%, P < 0.05) and 4 (-30%, P < 0.05), suggesting a direct transcriptional effect of PRMT4 also in hepatocytes[3].

临床研究
NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
NCT03742037	Systemic Lupus Erythematosus	Phase 2	Not yet recruiting	June 11, 2019	-

实验方案
	1mg	5mg	10mg
1 mM 5 mM 10 mM	2.18mL 0.44mL 0.22mL	10.90mL 2.18mL 1.09mL	21.81mL 4.36mL 2.18mL

参考文献

[1]Yilong Wang, Shu Yan,et al. PRMT4 promotes ferroptosis to aggravate doxorubicin-induced cardiomyopathy via inhibition of the Nrf2/GPX4 pathway. Cell Death Differ. 2022 Apr 5. [2] Yiheng Zhang, Robin A F Verwilligen,et al. PRMT4 inhibitor TP-064 impacts both inflammatory and metabolic processes without changing the susceptibility for early atherosclerotic lesions in male apolipoprotein E knockout mice. Atherosclerosis. 2021 Dec;338:23-29. [3]Yiheng Zhang, Miriam de Boe,et al. PRMT4 inhibitor TP-064 inhibits the pro-inflammatory macrophage lipopolysaccharide response in vitro and ex vivo and induces peritonitis-associated neutrophilia in vivo.Biochim Biophys Acta Mol Basis Dis. 2021 Nov 1;1867(11):166212.