CCT137690
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.
CCT137690是aurora激酶的可口服抑制剂,IC50值范围介于15至25 nM[1]。
Aurora激酶是一类丝氨酸/苏氨酸激酶,Aurora A、 Aurora B 和Aurora C在有丝分裂的调节中发挥重要作用,参与肿瘤的发生和发展,包括卵巢癌、乳腺癌、神经胶质瘤和结肠癌。因此aurora激酶被视为化疗中的抗癌靶标。CCT137690是aurora激酶的选择性小分子抑制剂,在体外和体内发挥抗肿瘤活性。除此之外,CCT137690促进小鼠肝微粒体的稳定性[1]。
在94个激酶的实验中,1 μM CCT137690可抑制80%的VEG-FR、aurora-A和FGF-R1的活性。CCT137690抑制aurora-B诱发的组蛋白H3的磷酸化。CCT137690对aurora-B和C的IC50值分别为25和19 nM。CCT137690具有有效的抗肿瘤增殖作用,例如A2780卵巢癌细胞(IC50值为140 nM),SW620(IC50值为300 nM)和SW48结肠癌(IC50值为157 nM)。它可以引起细胞周期的紊乱。此外,CCT137690与放疗有协同效应。它增加了SW620细胞对辐射的敏感性,两种方法联合治疗导致更多的凋亡性细胞死亡[1,2]。
在SW620异种移植小鼠模型中,CCT137690减慢了肿瘤的生长,且没有毒性。75 mg/kg的药物剂量导致治疗组肿瘤重量为对照组的37%。除此之外,CCT137690显著降低MYCN转基因小鼠神经母细胞瘤肿瘤重量,这意味着CCT137690对于MYCN扩增神经细胞瘤的患者具有治疗效果[1,3]。
参考文献:
[1] Bavetsias V, Large J M, Sun C, et al. Imidazo [4, 5-b] pyridine derivatives as inhibitors of Aurora kinases: lead optimization studies toward the identification of an orally bioavailable preclinical development candidate. Journal of medicinal chemistry, 2010, 53(14): 5213-5228.
[2] Wu X, Liu W, Cao Q, et al. Inhibition of Aurora B by CCT137690 sensitizes colorectal cells to radiotherapy. J ExpClin Cancer Res, 2014, 33(1): 13.
[3] Faisal A, Vaughan L, Bavetsias V, et al. The aurora kinase inhibitor CCT137690 downregulates MYCN and sensitizes MYCN-amplified neuroblastoma in vivo. Molecular cancer therapeutics, 2011, 10(11): 2115-2123
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 551.48 |
Cas No. | 1095382-05-0 |
Formula | C26H31BrN8O |
Solubility | insoluble in H2O; insoluble in EtOH; ≥6.89 mg/mL in DMSO |
Chemical Name | 3-[[4-[6-bromo-2-[4-(4-methylpiperazin-1-yl)phenyl]-1H-imidazo[4,5-b]pyridin-7-yl]piperazin-1-yl]methyl]-5-methyl-1,2-oxazole |
SDF | Download SDF |
Canonical SMILES | CC1=CC(=NO1)CN2CCN(CC2)C3=C4C(=NC=C3Br)N=C(N4)C5=CC=C(C=C5)N6CCN(CC6)C |
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。 |
描述 | CCT137690是一种高选择性和可口服的Aurora A、 Aurora B 和Aurora C抑制剂,IC50分别为15 nM,25 nM和19 nM。 | |||||
靶点 | Aurora A | Aurora B | Aurora C | |||
IC50 | 15 nM | 25 nM | 19 nM |