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。

使用AbMole产品发表的文献

• Am J Pathol. 2024 Feb;S0002-9440(24)00046-4.

  IL-6 Up-Regulates Expression of LIM-Domain Only Protein 4 in Psoriatic Keratinocytes through Activation of the MEK/ERK/NF-κB Pathway

• Cancer Biol Ther. 2024 Dec 31;25(1):2332000.

  The effects of Aurora Kinase inhibition on thyroid cancer growth and sensitivity to MAPK-directed therapies

• Open Life Sci. 2023 Oct 3;18(1):20220692.

  ErbB4 promotes M2 activation of macrophages in idiopathic pulmonary fibrosis

• Mol Cancer. 2022 Mar 18;21(1):77.

  Cholesterol promotes EGFR-TKIs resistance in NSCLC by inducing EGFR/Src/Erk/SP1 signaling-mediated ERRα re-expression

• Phytomedicine. 2022 Jun;100:154068.

  Geniposide alleviates VEGF-induced angiogenesis by inhibiting VEGFR2/PKC/ERK1/2-mediated SphK1 translocation

• Cancer Immunol Res. 2020 Oct;8(10):1273-1286.

  An IL6-Adenosine Positive Feedback Loop between CD73 + γδTregs and CAFs Promotes Tumor Progression in Human Breast Cancer

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

  JuBei Oral Liquid Induces Mitochondria-Mediated Apoptosis in NSCLC Cells

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

  Lateral Inhibition in Cell Specification Mediated by Mechanical Signals Modulating TAZ Activity.

• Acta Pharmacol Sin. 2019 Dec 17.

  Acid sphingomyelinase downregulation alleviates vascular endothelial leptin resistance in rats.

• J Neurosci. 2018 Mar 26.

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

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

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

产品使用成果展示

	数据来源	J Neurosci (2018). Figure 7. SCH772984 (Abmole Bioscience)
	方法	QRT-PCR
	细胞系/动物模型	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/动物模型
	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/动物模型
	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).

实验参考

体外实验*
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

*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。

体内实验*
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

*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。

化学性质

分子量	587.67
分子式	C33H33N9O2
CAS号	942183-80-4
溶解性（25°C）	DMSO 12 mg/mL warming
储存条件	粉末型式       -20°C   3年；4°C   2年 溶于溶剂       -80°C   6个月；-20°C   1个月
运输方式	冰袋运输，根据产品的不同，可能会有相应调整。

储备液配制

*下述溶液配置方法仅为基于分子量计算出的理论值。不同产品在配置溶液前，需考虑其在不同溶剂中的溶解度限制。

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

不同实验动物依据体表面积的等效剂量转换表（参考来源于公开文献）

	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，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的K_m系数（3），再除以大鼠的K_m系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。

参考文献

[1] Morris EJ, et al. Cancer Discov. Discovery of a Novel ERK Inhibitor with Activity in Models of Acquired Resistance to BRAF and MEK Inhibitors.