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| 活性类型 | 活性值-log(M) | 作用机制 | 期刊 | 参考文献(PubMed IDs) |
|---|
MK-5108 (VX-689), 丝氨酸/苏氨酸蛋白激酶 Aurora-A 抑制剂
有货
为什么选择此级别
Moligand™ 级 ，适用于对基线干扰要求严格的色谱和分析工作流程。
储存与运输
-80℃储存。特低温运输 。请查阅批次 COA 获取详细规格。
质量文档
SDS、COA、产品数据表及规格说明书均可下载。可通过批号查询获取批次 COA。
文献证明
在色谱分析、有机合成和交叉偶联反应领域已被 0 篇同行评审文献引用。
概述
MK-5108也叫VX-689，是一种新型有效选择性Aurora A激酶（AAK）抑制剂，通过竞争性结合AAK的ATP结合位点，有效抑制AAK活性，IC50值为0.064 nM。MK-5108对Aurora家族的其他激酶也有抑制作用，作用于Aurora B激酶的IC50值为14 nM，Aurora C激酶的IC50值为12 nM。MK-5108已被广泛研究，发现其对各种癌症包括乳腺癌、宫颈癌、结直肠癌、卵巢癌和胰腺癌均具有抗肿瘤活性。
Information
MK-5108 (VX-689) is a highly selectiveAurora Ainhibitor withIC50of 0.064 nM in a cell-free assay and is 220- and 190-fold more selective for Aurora A than Aurora B/C, while it inhibits TrkA with less than 100-fold selectivity. MK-5108 (VX-689) inducesauto
In vitro
MK-5108 inhibits Aurora-A activity in an ATP-competitive manner. MK-5108 shows robust selectivity against the other family kinases Aurora-B (220-fold) and Aurora-C (190-fold) in the biochemical assay. MK-5108 also reveals high selectivity for Aurora-A over other protein kinases. MK-5108 inhibits only one kinase (TrkA) with <100-fold selectivity. MK-5108 may be more Aurora-A selective than MLN8054. Consistent with the induction of pHH3-positive cells, MK-5108 induces accumulation of cells in the G2-M phase. MK-5108 inhibits the proliferation of tumor cells including HCC1143, AU565, MCF-7, HCC1806 and CAL85-1 with an IC50 of 0.42 μM, 0.45 μM, 0.52 μM, 0.56μM and 0.74 μM, respectively. MK-5108 decreases cell viability in a dose-dependent fashion in all three cell lines including LEIO285, LEIO505 and SK-LSM1 cells with an IC50 of approximately 100 nM. Incubation with MK-5108 in LEIO285 increases the proportion of cells in G2/M at 48 and 72 hours post-treatment. MK-5108 significant increases in Caspase 3/7 activity when compared to DMSO-treated control cultures at both time points. In LEIO505 cells, MK-5108 leads to more cells accumulating at G2/M phases at 24 hours but not 48 hours or 72 hours. MK-5108 arrests ULMS cell lines at M phase MK-5108 decreases the IC50 of gemcitabine in LEIO285 cells, but increases IC50 of gemcitabine in LEIO505 and SK-LMS1 cells.
In vivo
MK-5108 induces pHH3-positive cells at doses of 16 mg/kg and 32 mg/kg. Plasma concentration of MK-5108 at 8 mg/kg and 16 mg/kg are 1.7 μM and 4.4 μM, respectively. MK-5108 treatment results in the induction of pHH3 in tumor and skin tissues, which starts at 2 hours and reachs a maximum at 4 hours. MK-5108 treatments at 15 mg/kg and 30 mg/kg results in significant tumor growth inhibition with the change in mean tumor volume for the treatment group as a percentage of the mean change in the control group (%T/C) of 10% and −6% at day 11, and 17% and 5% at day 18, respectively. MK-5108 is well tolerated at both doses, with minimal reduction in body weight. MK-5108 also exhibits significant antitumor activity through intermittent dosing in nude rats bearing SW48 tumors, MK-5108 at 15 mg/kg and 45 mg/kg causes dose-dependent tumor growth inhibition with a %T/C of 35% and 7% at day 10, and 58% and 32% at day 27, respectively.
Cell Data
cell lines：
Concentrations：0 μM -1 μM
Incubation Time：12 hours
Powder Purity:≥97%
规格
英文别名
trans-4-(3-chloro-2-fluorophenoxy)-1-[[6-(2-thiazolylamino)-2-pyridinyl]methyl]-cyclohexanecarboxylic acid
规格或纯度
Moligand™, 10mM in DMSO
英文名称
MK-5108 (VX-689)
生化机理
MK-5108 (VX-689) 是一种高选择性 Aurora A 抑制剂，在无细胞实验中的 IC50 为 0.064 nM，对 Aurora A 的选择性分别是 Aurora B/C 的 220 倍和 190 倍，而对 TrkA 的抑制选择性不到 100 倍。MK-5108 (VX-689) 能诱导自噬。第一阶段
储存条件
-80℃储存
运输条件
特低温运输
作用类型
抑制剂
作用机制
丝氨酸/苏氨酸蛋白激酶 Aurora-A 抑制剂
名称和识别符
分子类型
小分子
Isomeric SMILES
C1CC(CCC1OC2=C(C(=CC=C2)Cl)F)(CC3=NC(=CC=C3)NC4=NC=CS4)C(=O)O
分子量
461.94
Reaxy-Rn
24898269
Reaxys-RN link address
https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=24898269&ln=
技术文档
高级数据
产品属性
| ALogP | 5.4 |
|---|
关联靶点（人）
IRAK3
Tchem
白细胞介素-1受体相关激酶3(Interleukin-1 receptor-associated kinase 3)
(1 活性数据)
TNK1
Tchem
非受体酪氨酸蛋白激酶 TNK1(Non-receptor tyrosine-protein kinase TNK1)
(1 活性数据)
BCR
Tclin
断点簇区域蛋白质(Breakpoint cluster region protein)
(1 活性数据)
AURKA
Tchem
极光激酶A(Aurora kinase A)
(2 活性数据)
AURKB
Tchem
极光激酶B(Aurora kinase B)
(1 活性数据)
AURKC
Tchem
极光激酶C(Aurora kinase C)
(1 活性数据)
JAK2
Tclin
酪氨酸蛋白激酶JAK2(Tyrosine-protein kinase JAK2)
(1 活性数据)
化学和物理性质
溶解性
Solubility (25°C) In vitro DMSO: 11 mg/mL (35.21 mM); Ethanol: -1 mg/mL
质检证书（CoA,COO,BSE/TSE 和分析图谱)
C of A & Other Certificates(BSE/TSE, COO):
输入批号以搜索分析图谱:
溶液计算器
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