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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) |
|---|
Milciclib (PHA-848125), 神经生长因子受体 Trk-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
Information
Milciclib (PHA-848125) is a potent, ATP-competitiveCDKinhibitor for CDK2 withIC50of 45 nM. It is >3-fold more selective for CDK2 than CDK1, 2, 4, 5, and 7. Milciclib (PHA-848125) induces cell death through autophagy. Phase 2.
In vitro
PHA-848125 inhibits, although with lower potency, the activities of cyclin H/CDK7, cyclin D1/CDK4, p35/CDK5, as well as cyclin E/CDK2 and cyclin B/CDK1 with IC50 values of 0.15, 0.16, 0.265, 0.363, 0.398 μM, respectively. Thropomyosin receptor kinase A is also inhibited by PHA-848125 in the same nanomolar range as CDKs. In the most PHA-848125-sensitive cell line, PHA-848125 induces a concentration-dependent G(1) arrest. PHA-848125 also impairs phosphorylation of the retinoblastoma protein at CDK2 and CDK4 specific sites, reduces retinoblastoma protein and cyclin A levels, and increases p21(Cip1), p27(Kip1) and p53 expression. PHA-848125 is added to the cells 48 h after TMZ and cell growth is evaluated after 3 additional days of culture. A drug combination of TMZ, BG and PHA-848125 induces an additive or synergistic effect on cell growth, depending on the cell line. In the absence of BG, the combination is still more active than the single agents in cell lines moderately sensitive to TMZ, but comparable to PHA-848125 alone in the two TMZ-resistant cell lines. When TMZ plus BG are used in combination with PHA-848125 against cultured normal melanocytes, neither synergistic nor additive antiproliferative effects are observed.
In vivo
In the preclinical xenograft A2780 human ovarian carcinoma model, PHA-848125 reveals good efficacy and is well tolerated upon repeated daily treatments. Treatment of K-Ras(G12D)LA2 mice with PHA-848125 (40 mg/kg twice daily for 10 days) results in significant tumor growth inhibition at the end of the treatment and is accompanied by a reduction in the cell membrane turnover. On the other hand, following oral administration, PHA-848125 shows significant antitumor activity in various human xenografts, carcinogen-induced tumors and in disseminated primary leukemia models; the plasma concentrations in rodents being in the same range as those found inhibiting cancer cell proliferation.
Cell Data
cell lines：Bladder cancer cells
Concentrations：5.7 mg/mL
Incubation Time：2 hours
Powder Purity:≥99%
规格
别名
米尔西利布(PHA-848125)
英文别名
N,1,4,4-tetramethyl-8-(4-(4-methylpiperazin-1-yl)phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
规格或纯度
Moligand™, 10mM in DMSO
英文名称
Milciclib (PHA-848125)
生化机理
Milciclib （PHA-848125）是一种强效的 ATP 竞争性 CDK 抑制剂，对 CDK2 的 IC50 为 45 nM。它对 CDK2 的选择性是 CDK1、2、4、5 和 7 的 3 倍以上。Milciclib (PHA-848125) 可通过自噬诱导细胞死亡。第二阶段
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
神经生长因子受体 Trk-A 抑制剂
名称和识别符
分子类型
小分子
Isomeric SMILES
CC1(CC2=CN=C(N=C2C3=C1C(=NN3C)C(=O)NC)NC4=CC=C(C=C4)N5CCN(CC5)C)C
分子量
460.57
Reaxy-Rn
12121648
Reaxys-RN link address
https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=12121648&ln=
技术文档
高级数据
产品属性
| ALogP | 2.8 |
|---|
关联靶点（人）
CDK1
Tchem
细胞周期蛋白依赖性激酶 1(Cyclin-dependent kinase 1)
(1 活性数据)
CDK7
Tchem
细胞周期蛋白依赖性激酶 7(Cyclin-dependent kinase 7)
(2 活性数据)
ERCC2
Tchem
通用转录和DNA修复因子IIH解旋酶亚基XPD(General transcription and DNA repair factor IIH helicase subunit XPD)
(1 活性数据)
CDK9
Tchem
细胞周期蛋白依赖性激酶9(Cyclin-dependent kinase 9)
(1 活性数据)
CDK4
Tclin
细胞周期蛋白依赖性激酶4(Cyclin-dependent kinase 4)
(2 活性数据)
CDK2
Tchem
细胞周期蛋白依赖性激酶2(Cyclin-dependent kinase 2)
(3 活性数据)
CDK5
Tchem
细胞周期蛋白依赖性类激酶 5(Cyclin-dependent-like kinase 5)
(1 活性数据)
GAK
Tchem
细胞周期蛋白G相关激酶(Cyclin-G-associated kinase)
(1 活性数据)
BCR
Tclin
断点簇区域蛋白质(Breakpoint cluster region protein)
(1 活性数据)
WEE1
Tchem
Wee1 类蛋白激酶(Wee1-like protein kinase)
(2 活性数据)
WEE2
Tchem
Wee1 类蛋白激酶 2(Wee1-like protein kinase 2)
(1 活性数据)
CLK1
Tchem
双特异性蛋白激酶 CLK1(Dual specificity protein kinase CLK1)
(1 活性数据)
CLK4
Tchem
双特异性蛋白激酶 CLK4(Dual specificity protein kinase CLK4)
(1 活性数据)
NTRK1
Tclin
高亲和力神经生长因子受体(High affinity nerve growth factor receptor)
(1 活性数据)
化学和物理性质
溶解性
Solubility (25°C) In vitro DMSO: 63 mg/mL (199.14 mM); Ethanol: 34 mg/mL warmed with 50ºC Water: bath (107.47 mM); Water: Insoluble;
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
常见问题
「Moligand?」是什么？
「Moligand?」是阿拉丁科学的高端产品线之一，专为多个工作流程中的高纯度应用而设计。与同类工作流程中的标准级别相比，「Moligand?」产品通常具有更严格的规格、更严谨的 QC 以及更强的批间一致性。
本产品应如何储存？
请于?80 °C条件下保存。需超低温保存以维持规定的有效期。
本产品如何运输？
本产品采用干冰配冷袋冷冻运输。收货后请立即拆包，并按上述储存条件保存；处理干冰时请戴隔热手套并保持通风。
本产品的 CAS 号、分子式和分子量是多少？
本产品的 CAS 号为 802539-81-7，分子式为 C25H32N8O，分子量为 460.57 g/mol。
如何获取批次专用COA？
每个订单都会随附分析证书（COA），您也可以从账户订单历史中下载。如需订购前的COA，请联系您的客户代表，或使用PDP上的"申请COA"按钮——我们将提供代表性批次的COA。
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