NVP-CGM097
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.
Storage | Store at -20°C |
M.Wt | 659.26 |
Cas No. | 1313363-54-0 |
Formula | C38H47ClN4O4 |
Solubility | Soluble in DMSO |
Chemical Name | (S)-1-(4-chlorophenyl)-7-isopropoxy-6-methoxy-2-(4-(methyl(((1r,4S)-4-(4-methyl-3-oxopiperazin-1-yl)cyclohexyl)methyl)amino)phenyl)-1,2-dihydroisoquinolin-3(4H)-one |
SDF | Download SDF |
Canonical SMILES | CC(OC(C=C1[C@]2([H])C3=CC=C(Cl)C=C3)=C(OC)C=C1CC(N2C4=CC=C(N(C[C@@]5([H])CC[C@@](N(CC6=O)CCN6C)([H])CC5)C)C=C4)=O)C |
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 [1,2]: | |
细胞系 |
神经母细胞瘤细胞系,HCT116细胞 |
溶解方法 |
可溶于DMSO。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。 |
反应条件 |
24 h |
应用 |
NVP-CGM097与NVP-LDK378的组合使用促进ALK突变体和p53野生型神经母细胞瘤细胞系的凋亡。NVP-LDK378抑制ALK磷酸化,NVP-CGM097诱导这些细胞系中p53及其下游靶基因的表达。NVP-CGM097显著抑制表达野生型p53的细胞的增殖,同时与p53无效细胞具有35-58倍的差异。在野生型p53细胞中,NVP-CGM097显著诱导p53重新分配进入细胞核,IC50为0.224 μM。NVP-CGM097抑制HCT116(p53WT/WT)细胞,IC50为454 ± 136 nM。 |
动物实验 [1,3]: | |
动物模型 |
移植hCD45+/hCD19+细胞的NOD.SCID. IL2R-/-(NSG)小鼠,ALK突变型神经母细胞瘤模型,MDM2扩增的SJSA-1人肿瘤模型 |
给药剂量 |
静脉注射,30 mg/kg,每天 |
应用 |
在移植hCD45+/hCD19+细胞的NOD.SCID. IL2R-/-(NSG)小鼠中,CGM097最终诱导进行性白血病小鼠濒临死亡。在26小时时间点上,CGM097显著上调了11个基因的表达,包括典型的p53靶标BBC3、CDKN1A和MDM2。CGM097显著改善总体生存。NVP-LDK378和NVP-CGM097组合导致肿瘤完全消退,并在神经母细胞瘤异种移植模型中显著延长存活时间。NVP-CGM097抑制p53和MDM2之间的相互作用,并在MDM2扩增的SJSA-1人肿瘤模型中重新激活p53途径。NVP-CGM097(30 mg/kg)增加荷瘤大鼠的p21 mRNA水平。NVP-CGM097的日常治疗以剂量依赖性方式抑制大鼠的SJSA-1肿瘤生长。 |
注意事项 |
由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。 |
References: [1]. Wang H Q, Battalagine L, Liang J, et al. The Mdm2 inhibitor NVP-CGM097 enhances the anti-tumor activity of NVP-LDK378 in ALK mutant neuroblastoma models[J]. 2014. [2]. Holzer P, et al. Discovery of a Dihydroisoquinolinone Derivative (NVP-CGM097): A Highly Potent and Selective MDM2 Inhibitor Undergoing Phase 1 Clinical Trials in p53wt Tumors. J Med Chem. 2015 Aug 27;58(16):6348-58. [3]. Townsend E C, DeSouza T, Murakami M A, et al. The MDM2 Inhibitor NVP-CGM097 Is highly active in a randomized preclinical trial of B-cell acute lymphoblastic leukemia patient derived xenografts[J]. 2015. |