SCH772984
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
SCH772984,通过基于亲和力的质谱高通量平台而鉴定到,是一种新型有效的和ATP竞争性的ERK1和ERK2抑制剂,IC50值分别为4 nmol/L和1 nmol/L。尽管SCH772984具有I型和II型激酶抑制剂的行为,但在300个激酶的实验中,SCH772984只对7种激酶具有高选择性,包括CLK2、FLT4、GSG2、MAP4K4、MAPK1、MINK1、PRKD1和TTK,在1 μmol/L浓度时具有超过50%的抑制。研究结果表明,SCH772984在纳摩尔浓度时有效抑制含BRAF、NRAS和KRAS突变的肿瘤细胞的生长。
参考文献:
Morris EJ, Jha S, Restaino CR, Dayananth P, Zhu H, Cooper A, Carr D, Deng Y, Jin W, Black S, Long B, Liu J, Dinunzio E, Windsor W, Zhang R, Zhao S, Angagaw MH, Pinheiro EM, Desai J, Xiao L, Shipps G, Hruza A, Wang J, Kelly J, Paliwal S, Gao X, Babu BS, Zhu L, Daublain P, Zhang L, Lutterbach BA, Pelletier MR, Philippar U, Siliphaivanh P, Witter D, Kirschmeier P, Bishop WR, Hicklin D, Gilliland DG, Jayaraman L, Zawel L, Fawell S, Samatar AA. Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors. Cancer Discov. 2013 Jul;3(7):742-750
- 1. Jinchao Gao, Qingxiang Song, et al. "Intracerebral fate of organic and inorganic nanoparticles is dependent on microglial extracellular vesicle function." Nat Nanotechnol. 2024 Mar;19(3):376-386. PMID: 38158436
- 2. Shengliang Zhang, Lanlan Zhou, et al. "Small-molecule NSC59984 induces mutant p53 degradation through a ROS-ERK2-MDM2 axis in cancer cells." Mol Cancer Res. 2022 Jan 6. PMID: 34992144
- 3. Xin‐Li Liu, Wen‐Jing Liu, et al. "miR-506-loaded gelatin nanospheres target PENK and inactivate the ERK/Fos signaling pathway to suppress triple-negative breast cancer aggressiveness." Mol Carcinog. 2021 Aug;60(8):538-555. PMID: 34062009
- 4. Labuzan SA, Lynch SA, et al. "Inhibition of Protein Phosphatase Methylesterase 1 Dysregulates MAP Kinase Signaling and Attenuates Muscle Cell Differentiation." Gene. 2020;144515. PMID: 32112987
- 5. Liu B, Shen LJ, et al. "Automobile exhaust-derived PM(2.5) induces blood-testis barrier damage through ROS-MAPK-Nrf2 pathway in sertoli cells of rats." Ecotoxicol Environ Saf. 2020 Feb;189:110053. PMID: 31862514
- 6. Li J, Shi W, et al. "Activation of DR3 signaling causes loss of ILC3s and exacerbates intestinal inflammation." Nat Commun. 2019 Jul 29;10(1):3371. PMID: 31358760
- 7. White SM, Avantaggiati ML, et al. "YAP/TAZ Inhibition Induces Metabolic and Signaling Rewiring Resulting in Targetable Vulnerabilities in NF2-Deficient Tumor Cells." Dev Cell. 2019 May 6;49(3):425-443.e9. PMID: 31063758
- 8. Linnan Yang, Jing Sun, et al. "Synergetic Functional Nanocomposites Enhance Immunotherapy in Solid Tumors by Remodeling the Immunoenvironment." Advanced Science. 16 February 2019.
- 9. Wang Q, Zhi Y, et al. "Suppression of OSCC malignancy by oral glands derived-PIP identified by iTRAQ combined with 2D LC-MS/MS." J Cell Physiol. 2019 Jan 28. PMID: 30693510
- 10. Alhakeem SS, McKenna MK, et al. "Chronic Lymphocytic Leukemia-Derived IL-10 Suppresses Antitumor Immunity." J Immunol. 2018 Jun 15;200(12):4180-4189. PMID: 29712773
- 11. Li YY, Wu C, et al. "Degradation of AMPK-α1 sensitizes BRAF inhibitor-resistant melanoma cells to arginine deprivation." Mol Oncol. 2017 Dec;11(12):1806-1825. PMID: 29094484
- 12. Stark RJ, Koch SR, et al."Endothelial nitric oxide synthase modulates Toll-like receptor 4-mediated IL-6 production and permeability via nitric oxide-independent signaling." FASEB J. 2017 Oct 23. pii: fj.201700410R. PMID: 29061842
- 13. Ferraiuolo RM, Tubman J, et al. "The cyclin-like protein, SPY1, regulates the ERα and ERK1/2 pathways promoting tamoxifen resistance."Oncotarget. 2017 Apr 4;8(14):23337-23352. PMID: 28423577
- 14. Ying-Ying Li. "BRAF inhibitor (vemurafenib) resistance confers sensitivity to arginine deprivation in melanoma." University of Miami.May 2016.
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 587.67 |
Cas No. | 942183-80-4 |
Formula | C33H33N9O2 |
Synonyms | SCH 772984; SCH-772984 |
Solubility | insoluble in EtOH; insoluble in H2O; ≥14.7 mg/mL in DMSO with gentle warming |
Chemical Name | (3R)-1-[2-oxo-2-[4-(4-pyrimidin-2-ylphenyl)piperazin-1-yl]ethyl]-N-(3-pyridin-4-yl-1H-indazol-5-yl)pyrrolidine-3-carboxamide |
SDF | Download SDF |
Canonical SMILES | C1CN(CC1C(=O)NC2=CC3=C(C=C2)NN=C3C4=CC=NC=C4)CC(=O)N5CCN(CC5)C6=CC=C(C=C6)C7=NC=CC=N7 |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
细胞实验[1]: | |
细胞系 |
黑色素瘤细胞系(M408, M202, WM1366) |
溶解方法 |
该化合物在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月 |
反应条件 |
24 h,500 nM |
实验结果 |
用SCH772984处理敏感性M408,导致pRSK减少,pERK1/2消失,轻微诱导pMEK,而RSK、MEK、ERK 1/2或AKT的总含量没有变化。对于抗性M202,在24小时适度诱导pMEK,pERK和pRSK有一些降低。SCH772984可以上调 M408和WM1366的pAKT水平。 |
动物实验[2]: | |
动物模型 |
裸鼠 |
剂量 |
25 mg/kg,一日两次,腹腔注射 |
实验结果 |
在两个原位患者来源的人胰腺癌异种移植模型(Panc253和Panc265)中,评估CDK抑制剂dinaciclib与ERK抑制剂SCH772984共同使用的治疗效果,这些模型非常类似于人类胰腺癌的生理和病理状况。将2-3 mm3肿瘤外植体植入裸鼠的胰腺中,在进行随机分组和治疗之前使用超声成像来测量肿瘤大小(3D),在肿瘤生长至50-100 mm3时后开始治疗。与对照组相比,Dinaciclib (20 mg/kg, i.p., t.i.w.)和SCH772984 (25 mg/kg, i.p., b.i.d.)的共同使用显著抑制原发原位Panc265(82.5%,p < 0.001)和Panc253(95.7%,p<0.001)的生长,Panc265(94.9%,p<0.001)和Panc253(92.4%,p<0.02)的转移性病变的数目也有所下降。 |
注意事项 |
请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。 |
References: [1] Wong D J L, Robert L, Atefi M S, et al. Antitumor activity of the ERK inhibitor SCH722984 against BRAF mutant, NRAS mutant and wild-type melanoma[J]. Molecular cancer, 2014, 13(1): 194. [2] Hu C, Dadon T, Chenna V, et al. Abstract B263: Combined inhibition of cyclin-dependent kinases (Dinaciclib) and AKT (MK-2206) or ERK (SCH772984) dramatically blocks pancreatic tumor growth and metastases in patient-derived orthotopic xenograft models[J]. Molecular Cancer Therapeutics, 2013, 12(11 Supplement): B263-B263. |
描述 | SCH772984是一种新型特异性的ERK1/2抑制剂,IC50值分别为4 nM和1 nM。 | |||||
靶点 | ERK1 | ERK2 | ||||
IC50 | 4 nM | 1 nM |
质量控制和MSDS
- 批次: