CAS:475489-16-8
Storage:Powder:2-8℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year
Purity:≥98%
Appearance:White to off-white Solid
NVP-AEW541 是一种有效的 IGF-1R 抑制剂。
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NVP-AEW541CAS:475489-16-8
Storage:Powder:2-8℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year
Purity:≥98%
Appearance:White to off-white Solid
CAS | 475489-16-8 |
English Name | NVP-AEW541 |
Synonyms | AEW541 |
Molecular Formula | C27H29N5O |
Molecular Weight | 439.55 |
Solubility | Soluble in DMSO |
Purity | ≥98% |
Appearance | White to off-white Solid |
Storage | Powder:2-8℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year |
SMILES | NC1=C2C(N([C@@H]3C[C@@H](C3)CN4CCC4)C=C2C5=CC=CC(OCC6=CC=CC=C6)=C5)=NC=N1 |
Target Point | IGF-1R |
Passage | Protein Tyrosine Kinase/RTK |
Background | NVP-AEW541 is a potent IGF-1R inhibitor. |
Biological Activity | NVP-AEW541 是一种有效的 IGF-1R 抑制剂,IC50 为 0.15 μM,也抑制 InsR,IC50 为 0.14 μM[1-2]。 |
IC50 | 0.15 ±0.036μM(IGF-IR);0.14±0.039μM(InsR);0.42±0.11μM(Flt-3);2±0.61μM(PDGFR);2.4±0.38μM(c-Src);3.3±1.4μM(c-Kit)[1] |
In Vitro | NVP-AEW541抑制重组IGF-IR激酶结构域的体外激酶活性,IC50值为0.15μM,并且与重组InsR激酶结构域等效。 NVP-AEW541被证实对IGF-IR激酶具有活性(IC50 = 86nM),并且在细胞水平上显示出选择性。实际上,与结构相关的天然InsR(IC50 =2.3μM)相比,发现NVP-AEW541对天然IGF-IR的效力是27倍。 NVP-AEW541抑制IGF-I介导的存活,软琼脂和MCF-7细胞增殖,IC50分别为0.162μM,0.105μM和1.64μM[1]。 |
In Vivo | NVP-AEW541(20,30或50mg/kg)的口服给药导致NWT-21肿瘤异种移植物中基础和IGF-I诱导的受体以及PKB和MAPK磷酸化的消除[1]。 NVP-AEW541通过口服管饲[50mg/kg在0.2mL 25mM L -(+)- 酒石酸]中每天施用两次,连续14天。对照组类似地每天两次用0.2mL载体[25mM L -(+)- 酒石酸]处理。每周测量肿瘤体积和动物体重三次直至治疗结束。那时,处死动物并收集肿瘤并固定福尔马林用于组织学和免疫组织化学分析。在这两种情况下,NVP-AEW541治疗导致肿瘤缩小达到统计学显著性(分别为HTLA-230和SK-N-BE2c,P = 0.0156和P = 0.0111)[2]。 |
Cell Experiment | 将3000至6000个细胞/孔接种在96孔板中,总培养基体积为100μL/孔。之后24小时加入增加浓度的化合物,一式四份。 72小时后,通过加入25μL/孔戊二醛(20%)固定细胞,并在室温下孵育10分钟。然后用200μL/孔H 2 O洗涤细胞2次,并加入100μL亚甲基蓝(0.05%)。在室温下孵育10分钟后,将细胞用200μL/孔H 2 O洗涤3次。加入200μL/孔HCl(3%),并在平板振荡器上在室温下孵育30分钟后,在650nm处测量吸光度[1]。 |
Animal Experiment | 小鼠[1]使用雌性Harlan无胸腺裸鼠NWT-21细胞在DMEM(高葡萄糖,4.5g/L),10%FCS,1%L-谷氨酰胺和1%丙酮酸钠中生长。最初将5×10 6个细胞/动物皮下注射到5只小鼠的右侧。对于体内功效实验,切除500至800mm 3的肿瘤,并将非坏死区域切割成3×3×3mm的片段。将肿瘤片段在无菌PBS中洗涤,并将每只动物的一个肿瘤片段皮下移植到右侧腹中。每周三次测定肿瘤体积(长×宽×高×π/ 6)和体重。在治疗的第一天(第0天),通过分层选择治疗组(NVP-AEW541)和对照组(仅载体)(每组8只动物,每组平均肿瘤体积约95mm 3)。使用NVP-AEW541(20,30或50 mg/kg; 10 mL/kg溶于25 mM L(+)- 酒石酸,治疗组)或25 mM,每天7天/周治疗动物po L(+)- 酒石酸(对照组)。抗肿瘤活性表示为T/C%(处理动物的肿瘤体积的平均增加量除以对照动物的肿瘤体积的平均增加量乘以100)。当平均肿瘤体积为约1500mm 3时终止实验。 |
Kinase Experiment | 通过测量来自[γ33P] ATP(1000Ci/mmol)的33P掺入适当的底物中,在存在或不存在抑制剂的情况下测定蛋白激酶的活性。蛋白激酶测定在96孔板中在室温下在下文详述的条件下进行,并通过加入20μL125mMEDTA终止。随后,将30μL(c-Abl,c-Src,IGF-1R)或40μL(所有其他激酶)的反应混合物转移到用甲醇预浸5分钟的Immobilon-PVDF上,用水冲洗,然后浸泡用0.5%H 3 PO 4保持5分钟并安装在真空歧管上。在点样所有样品后,连接真空并用200μL0.5%H 3 PO 4冲洗每个孔。取出膜并在含有1%H 3 PO 4的振荡器上洗涤4次,用乙醇洗涤一次。干燥后,安装在Packard TopCount 96孔框架中,加入10μL/孔的Microscint,计数膜。在四种浓度(通常为0.01,0.1,1和10μM)下,通过线性回归分析每种化合物一式两份的抑制百分比来计算IC 50值。一个单位的蛋白激酶活性定义为1nmole的33P转移自[ γ33P]在37℃下每毫克蛋白质每分钟ATP对底物蛋白质的影响[1]。 |
Data Literature Source | [1]. García-Echeverría C,et al. In vivo antitumor activity of NVP-AEW541-A novel,potent,and selective inhibitor of the IGF-IR kinase. Cancer Cell. 2004 Mar;5(3):231-9. [2]. Tanno B,et al. Down-regulation of insulin-like growth factor I receptor activity by NVP-AEW541 has an antitumor effect on neuroblastoma cells in vitro and in vivo. Clin Cancer Res. 2006,12(22),6772-6780. |
Unit | Bottle |
Specification | 5mg |
NVP-AEW541 是一种有效的 IGF-1R 抑制剂。