BMS-833923
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.
BMS-833923是一种口服生物可利用的和选择性的Smoothened(SMO)拮抗剂,在NIH3T3细胞系的IC50值为5.8 nM [1]。
Hedgehog (Hh)信号传导是参与胚胎发育和成人组织维持及修复的关键途径。其由Hh配体、跨膜受体Patched 1和2、G蛋白偶联受体样蛋白SMO和胶质瘤相关癌基因转录因子GLI 1至3组成。Hh途径的异常活化,包括突变和表观遗传都与多种肿瘤细胞中肿瘤发生的多个方面相关联。作为一种smoothened抑制剂,BMS-833923可以阻断环巴胺(天然存在的SMO抑制剂)与SMO的结合。BMS-833923显示出强效的Hh途径抑制活性,在多个基于细胞的试验中IC50值为纳摩尔级。 BMS-833923还强效抑制髓母细胞瘤和胰腺癌异种移植模型中Hh通路 [1、2和3]。
体外,BMS-833923抑制表达野生型SMO或活化突变SMO的细胞系中GLI1和PTCH1的表达,IC50值的范围为6至35 nM。在基于FACS的结合试验中,BMS-833923剂量依赖性地抑制环巴胺结合至SMO,IC50值为21 nM。在食管腺癌细胞系OE19和OE33中, BMS-833923治疗显著降低细胞增殖,IC50值均为10 μM。此外,BMS-833923抑制多发性骨髓瘤细胞的生长和ALDH+癌症干细胞的比例。BMS-833923还抑制来自于血液恶性肿瘤患者的许多其他肿瘤细胞的生长,包括ALL、AML和CML [3,4]。
在髓母细胞瘤和胰腺癌异种移植动物模型中,单剂量口服给药BMS-833923显示强效的Hh信号途径抑制。在胃食管反流病大鼠模型中,10 mg/kg/日剂量的BMS -833923给药导致Barrett食管和食管腺癌发展降低35.7% [ 3和5 ]。
参考文献:
[1] Siu L L, Papadopoulos K P, Alberts S, et al. A first-in-human phase 1study of an oral hedgehog pathway antagonist, BMS-833923 (XL139), in subjects with advanced or metastatic solid tumors. Mol Cancer Ther, 2009, 8(12 Suppl): A55.
[2] Justilien V, Fields A P. Molecular Pathways: Novel Approaches for Improved Therapeutic Targeting of Hedgehog Signaling in Cancer Stem Cells. Clinical Cancer Research, 2015, 21(3): 505-513.
[3] Gendreau S B, Hawkins D, Ho C P, et al. Abstract B192: Preclinical characterization of BMS‐833923 (XL139), a hedgehog (HH) pathway inhibitor in early clinical development. Molecular Cancer Therapeutics, 2009, 8(12 Supplement): B192-B192.
[4] Zaidi A H, Komatsu Y, Kelly L A, et al. Smoothened inhibition leads to decreased proliferation and induces apoptosis in esophageal adenocarcinoma cells. Cancer investigation, 2013, 31(7): 480-489.
[5] Gibson M K, Zaidi A H, Davison J M, et al. Prevention of Barrett esophagus and esophageal adenocarcinoma by smoothened inhibitor in a rat model of gastroesophageal reflux disease. Annals of surgery, 2013, 258(1): 82-88.
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 473.57 |
Cas No. | 1059734-66-5 |
Formula | C30H27N5O |
Synonyms | BMS 833923;BMS833923;XL-139;XL139;XL 139 |
Solubility | ≥47.4 mg/mL in DMSO; insoluble in H2O; ≥5.14 mg/mL in EtOH with gentle warming and ultrasonic |
Chemical Name | N-[2-methyl-5-(methylaminomethyl)phenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide |
SDF | Download SDF |
Canonical SMILES | CC1=C(C=C(C=C1)CNC)NC(=O)C2=CC=C(C=C2)NC3=NC4=CC=CC=C4C(=N3)C5=CC=CC=C5 |
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 |
OE19(JROECL19)和OE33(JROECL33)食管腺癌(EAC)细胞系 |
溶解方法 |
该化合物在DMSO中的溶解度大于47.4 mg/mL。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 |
0-100 μM,24和48小时 |
应用 |
在OE19和OE33细胞中,BMS-833923(10 μM)抑制细胞增殖,IC50为10 μM。BMS-833923(25 μM)完全抑制细胞增殖。在OE19和OE33细胞中,BMS-833923(10 μM)处理分别产生82和73.4%的凋亡细胞。 |
动物实验 [2,3]: | |
动物模型 |
成神经管细胞瘤和胰腺癌异种移植小鼠模型,具有胃食管反流病的雄性Sprague-Dawley大鼠 |
给药剂量 |
口服,10 mg/kg |
应用 |
在成神经管细胞瘤和胰腺癌异种移植物动物模型中,单次口服给药BMS-833923抑制Hh通路。在具有胃食管反流病的大鼠模型中,10 mg/kg/day的剂量的BMS-833923导致巴雷特食管和食管腺癌的发展减少35.7%。 |
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]. Zaidi A H, Komatsu Y, Kelly L A, et al. Smoothened inhibition leads to decreased proliferation and induces apoptosis in esophageal adenocarcinoma cells. Cancer investigation, 2013, 31(7): 480-489. [2]. Gendreau S B, Hawkins D, Ho C P, et al. Abstract B192: Preclinical characterization of BMS‐833923 (XL139), a hedgehog (HH) pathway inhibitor in early clinical development. Molecular Cancer Therapeutics, 2009, 8(12 Supplement): B192-B192. [3].Gibson M K, Zaidi A H, Davison J M, et al. Prevention of Barrett esophagus and esophageal adenocarcinoma by smoothened inhibitor in a rat model of gastroesophageal reflux disease. Annals of surgery, 2013, 258(1): 82-88. |
Description | BMS-833923是一种口服生物可利用的Smoothened小分子抑制剂,IC50值为6-35 nM。 | |||||
靶点 | Smoothened | |||||
IC50 | 6-35 nM |
质量控制和MSDS
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