SCH772984

生物活性

SCH772984是一种新型特异性的ERK1/2抑制剂， IC50分别为4 nM和1 nM。SCH772984是新型，选择性，ATP竞争性的ERK1/2抑制剂。SCH772984抑制ERK底物p90核糖体S6激酶（T359/S363 磷酸化-RSK）的磷酸化，这种作用存在剂量依赖性。SCH772984也能抑制ERK自身活化环中残基的磷酸化。

实验操作 来自于公开的文献，仅供相同实验参考（如实验材料、目的不同，请参考其他文献）

细胞实验
细胞系	BRAF- or RAS-mutant tumor cells
方法	Cell proliferation experiments were carried out in a 96-well format (six replicates), and cells were plated at a density of 4,000 cells per well. At 24 hours after cell seeding, cells were treated with DMSO or a 9-point IC50 dilution (0.001–10 μmol/L) at a final concentration of 1% DMSO for all concentrations. Viability was assayed 5 days after dosing using the ViaLight luminescence kit (Lonza) following the manufacturer's recommendations (n = 6, mean ± SE). For the cell line panel viability assay, cells were treated with SCH772984 for 4 days and assayed by the CellTiterGlo luminescent cell viability assay (Promega).
浓度	0.001–10 μmol/L
处理时间	4 days

动物实验
动物模型	Female nude mice bearing human LOX BRAF-mutant/MiaPaCa KRAS-mutant pancreatic/ melanoma xenograft model
配制	normal saline
剂量	12.5, 25, or 50 mg/kg for 14 days
给药处理	intraperitoneally

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）

	小鼠	大鼠	兔	豚鼠	仓鼠	狗
重量 (kg)	0.02	0.15	1.8	0.4	0.08	10
体表面积 (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km 系数	3	6	12	8	5	20

动物 A (mg/kg) = 动物 B (mg/kg) ×	动物 B的Km系数
	动物 A的Km系数

例如，依据体表面积折算法，将白藜芦醇用于小鼠的剂量22.4 mg/kg 换算成大鼠的剂量，需要将22.4 mg/kg 乘以小鼠的K_m系数（3），再除以大鼠的K_m系数（6），得到白藜芦醇用于大鼠的等效剂量为11.2 mg/kg。

化学数据

储备液配制

以下数据基于产品分子量，对于特殊产品，请参照COA中的储备液配制条件和说明进行操作。

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.7016 mL	8.5082 mL	17.0164 mL
5 mM	0.3403 mL	1.7016 mL	3.4033 mL
10 mM	0.1702 mL	0.8508 mL	1.7016 mL

使用AbMole产品发表的文献

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  Onco Targets Ther. 2020 Jul 31;13:7585-7598.

  JuBei Oral Liquid Induces Mitochondria-Mediated Apoptosis in NSCLC Cells
  SCH772984购买自AbMole

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  Acta Pharmacol Sin. 2019 Dec 17.

  Acid sphingomyelinase downregulation alleviates vascular endothelial leptin resistance in rats.
  SCH772984购买自AbMole

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  Cell. 2019 Mar 7;176(6):1379-1392.e14.

  Lateral Inhibition in Cell Specification Mediated by Mechanical Signals Modulating TAZ Activity.
  SCH772984购买自AbMole

• 

  J Neurosci 2018 Mar 26.

  HIPK2-mediated transcriptional control of NMDA receptor subunit expression regulates neuronal survival and cell death
  SCH772984购买自AbMole

• 

  Saudi Pharmaceutical Journal. 2016 May;24(3):354-62.

  Analgesic effect and possible mechanism of SCH772984 intrathecal injection on rats with bone cancer pain.
  SCH772984购买自AbMole

客户产品验证及相关生物数据

	数据来源	J Neurosci (2018). Figure 7. SCH772984 (Abmole Bioscience)
	方法	QRT-PCR
	细胞系	Primary cortical neurons
	浓度	5 nM, 50 nM
	处理时间	4 h
	实验结果	These results suggested that in addition to the increase in GluN2A protein levels in the synaptosomes and mitochondria, additional unknown mechanism(s), which could up-regulate the ERK-CREB signaling, might also contribute to the resistance of Hipk2-/- DA neurons to CCCP.

	数据来源	Saudi Pharmaceutical Journal (2016) . Figure 2.SCH772984, produced by AbMole
	方法	MWT determination
	细胞系
	浓度	0, 0.1, 1, 10μg
	处理时间	3, 6, 9, 12, 15, 18 and 24 hr
	实验结果	Comparing model group with Sham group and intrathecal tube group, MWT shows no significant differences at different time (p>0.05); comparing model group with BCP group and intrathecal tube +BCP group, MWT shows significant differences at different time (p<0.05); comparing model group with BCP group, MWT shows significant differences (p<0.05); comparing BCP group and intrathecal tube +BCP group, MWT shows no significant differences (p>0.05).

	数据来源	Saudi Pharmaceutical Journal (2016) . Figure 1.SCH772984, produced by AbMole
	方法	MWT determination
	细胞系
	浓度	0, 0.1, 1, 10μg
	处理时间	3, 6, 9, 12, 15, 18 and 24 hr
	实验结果	Comparing model group with Sham group and intrathecal tube group, MWT shows no significant differences at different time (p>0.05); comparing model group with BCP group and intrathecal tube +BCP group, MWT shows significant differences at different time (p<0.05); comparing model group with BCP group, MWT shows significant differences (p<0.05); comparing BCP group and intrathecal tube +BCP group, MWT shows no significant differences (p>0.05).

参考文献

Discovery of a Novel ERK Inhibitor with Activity in Models of Acquired Resistance to BRAF and MEK Inhibitors.
Morris EJ, et al. Cancer Discov. 2013 Jul;3(7):742-50. PMID: 23614898.