PHA-848125

目录号 M3519 所有产品仅供科研使用，严禁用于人或动物的治疗等任何其他用途，不为任何个人提供产品和服务

Milciclib (PHA-848125)是一种有效的，ATP竞争性CDK抑制剂，作用于CDK2，IC50为45 nM，作用于CDK2比作用于CDK1， 2， 4， 5和7选择性高3倍以上。

别名：Milciclib

规格	价格	库存状态
5mg	¥ 1760	中国库存现货
10mg	¥ 2600	中国库存现货
50mg	¥ 7680	中国库存现货

其他规格数量报价？

质量标准及产品资料

纯度： >98%
COA
MSDS

产品信息

生物活性

Milciclib (PHA-848125)是一种有效的，ATP竞争性CDK抑制剂，作用于CDK2，IC50为45 nM，作用于CDK2比作用于CDK1， 2， 4， 5和7选择性高3倍以上。PHA-848125有效抑制细胞周期蛋白(cyclin)A/CDK2, IC50为45 nM，PHA-84812为ATP竞争性抑制剂。PHA-848125也抑制cyclin H/CDK7,cyclin D1/CDK4,p35/CDK5,cyclin E/CDK2，及cyclin B/CDK1活性，IC50 分别为of 0.15, 0.16, 0.265, 0.363, 0.398 μM。PHA-848125作用于大部分对PHA-848125敏感的细胞系时，诱导细胞周期停在G1期，这种抑制存在浓度依赖性。

使用AbMole产品发表的文献

Fish Physiol Biochem. 2019 Dec;45(6):1829-1843.

A novel CDK-2 homolog identified in lamprey, Lampetra japonica, with roles in apoptosis.

实验参考

体外实验*
细胞系	Melanoma cells
方法	Suspending melanoma cells in culture media at a concentration of 2 × 10⁴ cells/mL, dispensing in 50 μL aliquots into flat-bottom 96-well plates and allowed to adhere overnight at 37 °C. Then adding Graded amounts of PHA-848125 or TMZ to the wells (4 wells per point) in 50 μL of CM and incubating the plates 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, adding 10 μM BG 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, using the MTT assay to evaluate cell growth . 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).
浓度	5.7 mg/mL
处理时间	2 hours

*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。

体内实验*
动物模型	K-Ras(G12D)LA2 mice
配制	5% dextrose solution
剂量	40 mg/kg twice daily for 10 days
给药处理	Oral administration

*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。

化学性质

分子量	460.57
分子式	C25H32N8O
CAS号	802539-81-7
溶解性（25°C）	DMSO 90 mg/mL
储存条件	粉末型式 -20°C 3年；4°C 2年溶于溶剂 -80°C 6个月；-20°C 1个月
运输方式	冰袋运输，根据产品的不同，可能会有相应调整。

储备液配制

*下述溶液配置方法仅为基于分子量计算出的理论值。不同产品在配置溶液前，需考虑其在不同溶剂中的溶解度限制。

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	2.1712 mL	10.8561 mL	21.7122 mL
5 mM	0.4342 mL	2.1712 mL	4.3424 mL
10 mM	0.2171 mL	1.0856 mL	2.1712 mL

不同实验动物依据体表面积的等效剂量转换表（参考来源于公开文献）

	小鼠	大鼠	兔	豚鼠	仓鼠	狗
重量 (kg)	0.02	0.15	1.8	0.4	0.08	10
体表面积 (m²)	0.007	0.025	0.15	0.05	0.02	0.5
K_m 系数	3	6	12	8	5	20

动物 A (mg/kg) = 动物 B (mg/kg) ×	动物 B的K_m系数
	动物 A的K_m系数

例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的K_m系数（3），再除以大鼠的K_m系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。

参考文献

[1] C Albanese, et al. Anti-tumour efficacy on glioma models of PHA-848125, a multi-kinase inhibitor able to cross the blood-brain barrier

[2] Simona Caporali, et al. Down-regulation of the PTTG1 proto-oncogene contributes to the melanoma suppressive effects of the cyclin-dependent kinase inhibitor PHA-848125

[3] Anna Degrassi, et al. Efficacy of PHA-848125, a cyclin-dependent kinase inhibitor, on the K-Ras(G12D)LA2 lung adenocarcinoma transgenic mouse model: evaluation by multimodality imaging

[4] Simona Caporali, et al. The cyclin-dependent kinase inhibitor PHA-848125 suppresses the in vitro growth of human melanomas sensitive or resistant to temozolomide, and shows synergistic effects in combination with this triazene compound

[5] Maria Gabriella Brasca, et al. Identification of N,1,4,4-tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (PHA-848125), a potent, orally available cyclin dependent kinase inhibitor

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