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CEP-18770

现货
Catalog No.
A4009
蛋白酶体抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,380.00
现货
5mg
¥ 1,050.00
现货
10mg
¥ 1,800.00
现货
50mg
¥ 6,400.00
现货
100mg
¥ 9,500.00
Ship with 10-15 days

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Background

CEP-18770 is a novel, potent and reversible P2 threonine boronic acid inhibitor of proteasome that inhibits proteasome’s chymotrypsin-like activity, with the value of inhibition constant IC50 of 3.8 nM, by down-modulating the activity of nuclear factor-KB (NF-KB) as well as the expression of a few NF-KB downstream effectors. Preliminary results of multiple studies have shown that CEP-18770 exerts potent antitumor activities against human multiple myeloma (MM) cell lines by inducing apoptotic cell death, exhibits a strong antiangiogenic activity suppressing RANKL-induced osteoclastogenesis, and displays a favorable cytotoxicity profile towards normal cells including epithelial cells, bone marrow progenitors, and bone marrow-derived stromal cells.

Reference

Piva R, Ruggeri B, Williams M, Costa G, Tamagno I, Ferrero D, Giai V, Coscia M, Peola S, Massaia M, Pezzoni G, Allievi C, Pescalli N, Cassin M, di Giovine S, Nicoli P, de Feudis P, Strepponi I, Roato I, Ferracini R, Bussolati B, Camussi G, Jones-Bolin S, Hunter K, Zhao H, Neri A, Palumbo A, Berkers C, Ovaa H, Bernareggi A, Inghirami G. CEP-18770: A novel, orally active proteasome inhibitor with a tumor-selective pharmacologic profile competitive with bortezomib. Blood. 2008;111(5):2765-2775

文献引用

1. Sha Z, Schnell HM, et al. "Rapid induction of p62 and GABARAPL1 upon proteasome inhibition promotes survival before autophagy activation." J Cell Biol. 2018 Mar 13. pii: jcb.201708168.  PMID:29535191

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt413.3
Cas No.847499-27-8
FormulaC21H28BN3O5
Solubility≥16.75 mg/mL in DMSO, ≥32.27 mg/mL in EtOH with ultrasonic, <2.47 mg/mL in H2O
Chemical Name[(1R)-1-[[(2S,3R)-3-hydroxy-2-[(6-phenylpyridine-2-carbonyl)amino]butanoyl]amino]-3-methylbutyl]boronic acid
SDFDownload SDF
Canonical SMILESB(C(CC(C)C)NC(=O)C(C(C)O)NC(=O)C1=CC=CC(=N1)C2=CC=CC=C2)(O)O
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。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。

试验操作

细胞实验[1]:

细胞系

RPMI-8226细胞

溶解方法

该化合物在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

40 nM,4到8 hours

实验结果

作为蛋白酶体的抑制剂,CEP-18770在4至8小时内诱导泛素化蛋白的积累,其特征与另一种蛋白酶体抑制剂bortezomib治疗后观察到的结果相似。

动物实验[1]:

动物模型

皮下异种移植人MM RPMI 8226的SCID小鼠

剂量

静脉内(1至6 mg/kg,2q7d×8次注射)或口服给药(溶于3%DMSO,10%Solutol和87%的无菌0.9%NaCl溶液),每周两次,剂量分别为7.8、10、13 mg/kg,以20 mL/kg的体积重量比。

实验结果

静脉内施用CEP-18770表现出持续的剂量相关的肿瘤重量抑制效果,在所有测试剂量下RTWI为100%。肿瘤移植后120天,3和4 mg/kg CEP-18770静脉内给药组内无肿瘤小鼠的发生率剂量相关性增加,分别为89%和80%。口服给药10 mg/kg CEP-18770显著降低肿瘤重量,肿瘤完全消退的发生率具有显著剂量相关性,产生75%的CR发生率和25%无肿瘤小鼠。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1] Piva R, Ruggeri B, Williams M, et al. CEP-18770: A novel, orally active proteasome inhibitor with a tumor-selective pharmacologic profile competitive with bortezomib. Blood, 2008, 111(5): 2765-2775.

生物活性

描述 CEP-18770是一种新型可口服的蛋白酶体糜蛋白酶样活性抑制剂,在细胞内的IC50值为3.8 nM。
靶点 proteasome          
IC50 3.8 nM          

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