ALW-II-41-27
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.
ALW-II-41-27是一种有效的EPH家族激酶抑制剂,作用于EPHA2,IC50值为11 nM[1] [2]。
EPH家族蛋白是疾病和正常发育的关键调节因子。EPH受体参与许多细胞内信号通路,如PI3K/AKT/mTOR、RAS/RAF/MAPK、FAK、SRC、ABL和RHO/RAC/CDC42[2]。
在H358细胞中,ALW-II-41-27以1 μM浓度处理后15分钟内可损害EPHA2受体的酪氨酸磷酸化,并持续抑制6小时。ALW-II-41-27也剂量依赖性地抑制配体诱导的EPHA2磷酸化。在RNAi消除EPHA2的NSCLC细胞系中,细胞对ALW-II-41-27不太敏感。
肺癌中的结果表明,EPHA2具有致癌作用。在非小细胞肺癌(NSCLCs)荷瘤小鼠中,ALW-II-41-27以15 mg/kg的剂量,每天2次腹腔注射,持续给药14天后显著抑制H358肿瘤的生长。与载体或NG-25治疗组相比,ALW-II-41-27显著增加肿瘤细胞的凋亡,这与EPHA2遗传消融的效应相似,但并没有引起血管密度或肿瘤细胞增殖的显著差异[2]。
参考文献:
[1]. Marialuisa Moccia, Qingsong Liu, Teresa Guida, et al. Identification of Novel Small Molecule Inhibitors of Oncogenic RET Kinase. PLOS ONE, 2015, 10(6):e0128364.
[2]. Katherine R. Amato, Shan Wang, Andrew K. Hastings, et al. Genetic and pharmacologic inhibition of EPHA2 promotes apoptosis in NSCLC. Journal of Clinical Investigation, 2014, 124(5):2037-2049.
- 1. Yutuan Wu, Jie Huang, et al. "MEK inhibition overcomes resistance to EphA2-targeted therapy in uterine cancer." Gynecol Oncol. 2021 Oct;163(1):181-190. PMID:34391578
- 2. Hao Wang, Wei Hou, et al. "Targeting EphA2 suppresses hepatocellular carcinoma initiation and progression by dual inhibition of JAK1/STAT3 and AKT signaling." Cell Rep. 2021 Feb 23;34(8):108765. PMID:33626345
- 3. Tessa Y.S. Le Large, Elisa Giovannetti, et al. "Microdissected pancreatic cancer proteomes reveal tumor heterogeneity and therapeutic targets." JCI Insight. 2020;5(15):e138290. PMID:32634123
- 4. Ishigaki H, Minami T, et al. "EphA2 inhibition suppresses proliferation of small-cell lung cancer cells through inducing cell cycle arrest." Biochem Biophys Res Commun. 2019 Sep 24. pii: S0006-291X(19)31803-0. PMID:31558317
- 5. Xi Y, Kim T, et al. "Local lung hypoxia determines epithelial fate decisions during alveolar regeneration." Nat Cell Biol.2017 Aug;19(8):904-914. PMID:28737769
Storage | Store at -20°C |
M.Wt | 607.69 |
Cas No. | 1186206-79-0 |
Formula | C32H32F3N5O2S |
Synonyms | Eph receptor tyrosine kinase inhibitor; |
Solubility | ≥60.8 mg/mL in EtOH; insoluble in H2O; ≥102 mg/mL in DMSO |
Chemical Name | N-(5-((4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)carbamoyl)-2-methylphenyl)-5-(thiophen-2-yl)nicotinamide |
SDF | Download SDF |
Canonical SMILES | CCN1CCN(CC2=C(C(F)(F)F)C=C(NC(C3=CC(NC(C4=CN=CC(C5=CC=CS5)=C4)=O)=C(C=C3)C)=O)C=C2)CC1 |
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 |
非小细胞肺癌(NSCLC)PC-9/ER、PC-9/ERC15、PC-9/ERC16细胞系 |
溶解方法 |
溶于DMSO。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。 |
反应条件 |
1 μM,72 h |
应用 |
1 μM的ALW-II-41-27抑制erlotinib耐药NSCLC细胞系的增殖,增加细胞凋亡。ALW-II-41-27诱导的细胞凋亡伴随着酶切caspase-3和PARP的增加以及抗细胞凋亡蛋白BCL-xL和MCL-1的表达降低。 |
动物实验[2]: | |
动物模型 |
6周龄的无胸腺裸鼠 |
剂量 |
腹腔注射,15、30 mg/kg,每天两次 |
应用 |
给药ALW-II-41-27显著抑制荷瘤小鼠的H358肿瘤生长。组织学分析显示,与使用NG-25或载体处理的肿瘤相比,ALW-II-41-27处理的肿瘤的凋亡显著增加,这与遗传消融EPHA2的作用类似。 |
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]. Amato K R, Wang S, Tan L, et al. EPHA2 blockade overcomes acquired resistance to EGFR kinase inhibitors in lung cancer[J]. Cancer research, 2016, 76(2): 305-318. [2]. Amato K R, Wang S, Hastings A K, et al. Genetic and pharmacologic inhibition of EPHA2 promotes apoptosis in NSCLC[J]. The Journal of clinical investigation, 2014, 124(5): 2037-2049. |
质量控制和MSDS
- 批次: