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Milciclib

产品编号 T6081 CAS 802539-81-7

别名: PHA-848125

Milciclib (PHA-848125) 是一种 ATP 竞争性的 CDK 和原肌球蛋白受体激酶双重抑制剂，作用于 CDK2，IC50 为 45 nM。

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Milciclib, CAS 802539-81-7

规格	价格/CNY	货期
1 mg	￥ 525	现货
5 mg	￥ 1,560	现货
10 mg	￥ 2,290	现货
25 mg	￥ 3,890	现货
50 mg	￥ 5,570	现货
100 mg	￥ 7,790	现货
1 mL * 10 mM (in DMSO)	￥ 1,720	现货

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其他形式的 Milciclib:

Milciclib maleate
询价

选择批次

纯度: 99.73%

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生物活性

化学信息

存储 & 溶解度

参考文献

相关产品

产品描述	Milciclib (PHA-848125) (PHA-848125) is a potent, ATP-competitive CDK inhibitor for CDK2 with IC50 of 45 nM. It is >3-fold more selective for CDK2 than CDK1, 2, 4, 5, and 7. Phase 2.
靶点活性	CDK2-CyclinA:45 nM
体外活性	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. [1] 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.[2] 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. [2] A drug combination of TMZ, BG and PHA-848125 induces an additive or synergistic effect on cell growth, depending on the cell line. [2] 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.[2]
体内活性	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.[3] 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.[4]
激酶实验	Biochemical kinase inhibition assays: Inhibition of kinase activity by PHA-848125 is assessed using a strong anion exchanger (Dowex 1X8 resin)–based assay in robotized format run on 384-well plates. In this assay, specific peptides or protein substrates are transphosphorylated by their specific kinase in the presence of ATP traced with [γ-33P]ATP using optimal buffers and cofactors. The potency of PHA-848125 toward CDKs and 38 additional kinases belonging to an in-house Kinase Selectivity Screening panel is evaluated, and the relevant IC50s are determined. For each enzyme, the absolute KM values for ATP and the specific substrate are calculated and each assay is then run at optimized ATP (2KM) and substrate (5KM) concentrations. This setting enables direct comparison of IC50 values of PHA-848125 across the panel for evaluation of its biochemical profile.
细胞实验	Melanoma cells are suspended in culture media at a concentration of 2 × 104 cells/mL, dispensed in 50 μL aliquots into flat-bottom 96-well plates and allowed to adhere overnight at 37 °C. Graded amounts of PHA-848125 or TMZ are then added to the wells (4 wells per point) in 50 μL of CM and the plates are incubated at 37 °C in a 5% CO2 humidified atmosphere for 5 days. The cytotoxic effects of TMZ are also evaluated in combination with the MGMT inhibitor BG. To this end, 10 μM BG is added to the plates 2 hours before TMZ and left in culture for the entire period of cell exposure to the drug. ContS1017rol groups are represented by untreated cells and cells treated with BG or DMSO alone. The growth of the cells treated with BG or DMSO alone does not differ from that of untreated cells. MGMT activity of BG-treated cells is undetectable 2 hours after the addition of the inhibitor PHA-848125 and remained essentially undetectable up to the end of the assay. Normal melanocytes are suspended in MGM at the concentration of 1.6 × 105 cells/mL, plated (50 μL/well) and exposed to TMZ + BG or to PHA-848125 as described for melanoma cells. At the end of the incubation period, cell growth is evaluated by the MTT assay. Briefly, 0.1 mg of MTT (in 20 μL of PBS) is added to each well and cells are incubated at 37 °C for 4 hours. Cells are then lysed with a buffer (0.1 mL/well) containing 20% SDS and 50% N,N-dimethylformamide, pH 4.7. After overnight incubation, the absorbance is read at 595 nm using a 3550-UV microplate reader. Cell sensitivity to drug treatment is expressed in terms of IC50 (drug concentration producing 50% inhibition of cell growth, calculated on the regression line in which absorbance values at 595 nm are plotted against the logarithm of drug concentration).(Only for Reference)

别名	PHA-848125
分子量	460.57
分子式	C25H32N8O
CAS No.	802539-81-7

存储

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度

H2O: < 1 mg/mL (insoluble or slightly soluble)

Ethanol: < 1 mg/mL (insoluble or slightly soluble)

DMSO: 85 mg/mL (184.6 mM)

溶液配制表

可选溶剂	浓度体积质量	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	2.1712 mL	10.8561 mL	21.7122 mL	54.2806 mL
	5 mM	0.4342 mL	2.1712 mL	4.3424 mL	10.8561 mL
	10 mM	0.2171 mL	1.0856 mL	2.1712 mL	5.4281 mL
	20 mM	0.1086 mL	0.5428 mL	1.0856 mL	2.714 mL
	50 mM	0.0434 mL	0.2171 mL	0.4342 mL	1.0856 mL
	100 mM	0.0217 mL	0.1086 mL	0.2171 mL	0.5428 mL

计算器

摩尔浓度计算器

稀释计算器

配液计算器

分子量计算器

质量

浓度

容积

分子量

浓度 (起始)

容积 (起始)

浓度 (终)

容积 (终)

溶液体积

质量

配液浓度

参考文献

1. Brasca MG, et al. J Med Chem. 2009, 52(16), 5152-5563. 2. Caporali S, et al. Pharmacol Res. 2010, 61(5), 437-448. 3. Degrassi A, et al. Mol Cancer Ther. 2010, 9(3), 673-681. 4. Albanese C, et al. Mol Cancer Ther. 2010, 9(8), 2243-2254.

文献引用

1. Wu Z, Huang Z, Zhou X, et al.Comprehensive analysis of cuproptosis genes and cuproptosis-related genes as prognosis factors in esophageal squamous cell carcinoma.Genomics.2023: 110732.

剂量换算

对于不同动物的给药剂量换算，您也可以参考 更多...

体内实验配液计算器

请在以下方框中输入您的动物实验信息后点击计算，可以得到母液配置方法和体内配方的制备方法：比如您的给药剂量是10 mg/kg，每只动物体重20 g，给药体积100 μL，一共给药动物10 只，您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。

母液配置方法：2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL)，如您需要配置的浓度超过该产品的溶解度，请先与我们联系。

体内配方的制备方法：取 50 μL DMSO 主液，加入 300 μL PEG300，混匀澄清，再加 50 μL Tween 80，混匀澄清，再加 600 μL ddH2O, 混匀澄清。

第一步：请输入动物实验的基本信息

剂量

mg/kg

每只动物体重

给药体积

μL

动物数量

第二步：请输入动物体内配方组成，不同的产品配方组成不同，如有配方需求，可先联系我们提供正确的体内配方。

% DMSO+

% +

% Tween 80+

% ddH₂O

%DMSO+

计算重置

计算结果如下:

工作液浓度: mg/ml;

母液配置方法: mg 药物溶于 μL DMSO (母液浓度为 mg/mL)，如您需要配置的浓度超过该产品的溶解度，请先与我们联系。

体内配方的制备方法：取 μL DMSO 主液，加入 μL PEG300，混匀澄清，再加 μL Tween 80，混匀澄清，再加 μL ddH₂O, 混匀澄清。

备注:

要按顺序从左向右依次添加助溶剂。可配合物理方法，如涡流、超声波或热水浴使之帮助溶解。

技术支持

您可能有的问题的答案可以在抑制剂处理说明中找到，包括如何准备库存溶液，如何存储产品，以及基于细胞的分析和动物实验需要特别注意的问题。

Keywords

Milciclib 802539-81-7 Autophagy Cell Cycle/Checkpoint Tyrosine Kinase/Adaptors Trk receptor CDK inhibit Cyclin dependent kinase PHA-848125 PHA 848125 Inhibitor PHA848125 inhibitor

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Milciclib

存储

溶解度

溶液配制表

计算器

输入分子式，点击计算，可计算出产品的分子量。

参考文献

文献引用

相关产品

相关化合物库

剂量换算

体内实验配液计算器

技术支持

Keywords