CAS:641571-10-0
Storage:Powder:2-8℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year
Purity:HPLC≥98%
Appearance:White to off-white Solid
Nilotinib是一种具有抗肿瘤活性的 Bcr-Abl 酪氨酸激酶抑制剂,可用于产生耐药的或不耐受的慢性髓性白血病的相关研究。
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NilotinibCAS:641571-10-0
Storage:Powder:2-8℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year
Purity:HPLC≥98%
Appearance:White to off-white Solid
CAS | 641571-10-0 |
Chinese Name | 尼洛替尼 |
English Name | Nilotinib |
Synonyms | AMN107;Tasigna |
Molecular Formula | C28H22F3N7O |
Molecular Weight | 529.52 |
Solubility | Soluble in DMSO ≥10mg/mL |
Purity | HPLC≥98% |
Appearance | White to off-white Solid |
Storage | Powder:2-8℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year |
EC | EINECS 700-544-5 |
MDL | MFCD09833716 |
SMILES | O=C(NC1=CC(C(F)(F)F)=CC(N2C=NC(C)=C2)=C1)C3=CC=C(C)C(NC4=NC=CC(C5=CC=CN=C5)=N4)=C3 |
Target Point | Bcr-Abl |
Passage | Protein Tyrosine Kinase/RTK |
Background | Nilotinib is a Bcr-Abl tyrosine kinase inhibitor with antitumor activity, which can be used for the study of drug-resistant or intolerant chronic myeloid leukemia. |
Biological Activity | Nilotinib是一种口服可用的具有抗肿瘤活性的 Bcr-Abl 酪氨酸激酶抑制剂。[1-5] |
In Vitro | 新型选择性Abl抑制剂Nilotinib(AMN107)设计用于与BCR-ABL的ATP结合位点相互作用,其亲和力高于伊马替尼。除了与伊马替尼相比显着更有效(IC50 <30 nM)外,尼罗替尼还能维持对大多数赋予伊马替尼耐药性的BCR-ABL点突变体的活性[1]。尼罗替尼显示出对抗GIST异种移植物系和伊马替尼抗性GIST细胞系的显着抗肿瘤效力。亲本细胞系GK1C和GK3C显示伊马替尼敏感性,IC50分别为4.59±0.97μM和11.15±1.48μM。伊马替尼耐药细胞系GK1C-IR和GK3C-IR显示伊马替尼耐药,IC50值分别为11.74±0.17μM(P <0.001)和41.37±1.07μM(P <0.001)[2]。 |
In Vivo | 在GK1X异种移植物系(ns)中,伊马替尼的肿瘤生长抑制百分比(TGI)为83.8%,尼罗替尼为69.6%。在GK2X异种移植物系中,伊马替尼的TGI为83.0%,尼罗替尼(ns)为85.3%。此外,伊马替尼的GK3X异种移植物线TGI为31.1%,尼罗替尼(ns)为47.5%。这些结果表明,除了GK1X异种移植物系外,尼罗替尼显示出与伊马替尼相当或更高的抗肿瘤作用[2]。尼罗替尼对宏观和微观病理评分具有显著的治愈作用,并确保吲哚美辛诱导的小肠结肠炎大鼠模型中相当大的粘膜愈合。虽然尼罗替尼降低了结肠中PDGFRα和β水平以及凋亡评分,但它对体重和TNF-α水平没有显著影响。进一步的实验研究可以为人类提供更明确的证据[3]。 |
Cell Experiment | 将人GIST细胞系GK1C和GK3C以及伊马替尼抗性细胞系GK1C-IR和GK3C-IR接种于96孔微量培养板中并培养12小时,然后暴露于伊马替尼(1-100μM)或尼罗替尼(1- 100μM)72小时。通过WST-8测定法定量细胞。光密度(OD)由Sunrise rainbow确定。抑制率计算如下:抑制%=(处理组 - 空白的OD)/(对照组 - 空白的OD)×100%。计算导致50%生长抑制的测试药物浓度(IC50)[2]。 |
Animal Experiment | 小鼠[2]使用裸鼠中的GIST异种移植物系GK1X,GK2X和GK3X。通过在BALB/cSLc-nu/nu小鼠中连续传代来维持这些异种移植物系。每天用载体或40mg/kg伊马替尼或尼罗替尼治疗携带GK1X,GK2X和GK3X肿瘤(每组6-8只小鼠)的小鼠,持续4周。根据公式LW2/2,根据肿瘤长度(L)和宽度(w)的厚度测量值确定肿瘤体积(TV)。电视每两到三天以及评估当天确定。处死小鼠并且如下计算肿瘤生长抑制(TGI)的百分比:TGI(%)= [1-(评估日的治疗组肿瘤体积 - 治疗组肿瘤体积在第1天的平均值)/(平均值)对照组肿瘤体积对第1天对照组肿瘤体积的评价日均值]]×100。大鼠[3]雌性Wistar白化大鼠,体重226-243g(平均体重,241.09g),用于本研究。以吲哚美辛给药的同一天开始,通过口胃管向Nilotinib组大鼠(n = 7)施用尼罗替尼,以两个分剂量施用20mg/kg/d,持续13天。在13-d期结束时,在乙醚麻醉下从所有大鼠获得用于病理学检查的血液和组织样品。然后通过断头处死所有动物。 |
Data Literature Source | [1]. Weisberg E,et al. Beneficial effects of combining nilotinib and imatinib in preclinical models of BCR-ABL+ leukemias. Blood. 2007 Mar 1;109(5):2112-20. [2]. Sako H,et al. Antitumor effect of the tyrosine kinase inhibitor Nilotinib on gastrointestinal stromal tumor (GIST) and Imatinib-resistant GIST cells. PLoS One. 2014 Sep 15;9(9):e107613. [3]. Dervis Hakim G,et al. Mucosal healing effect of nilotinib in indomethacin-induced enterocolitis: A rat model. World J Gastroenterol. 2015 Nov 28;21(44):12576-85. [4]. Fujita KI,et al. Involvement of the Transporters P-Glycoprotein and Breast Cancer Resistance Protein in Dermal Distribution of the Multikinase Inhibitor Regorafenib and Its Active Metabolites. J Pharm Sci. 2017 Sep;106(9):2632-2641. [5]. Meirson T,et al. Targeting invadopodia-mediated breast cancer metastasis by using ABL kinase inhibitors. Oncotarget. 2018 Apr 24;9(31):22158-22183. |
Unit | Piece |
Specification | 50mg 10mM*1mL in DMSO 100mg |
Nilotinib是一种具有抗肿瘤活性的 Bcr-Abl 酪氨酸激酶抑制剂,可用于产生耐药的或不耐受的慢性髓性白血病的相关研究。