PF-670462
(Synonyms: 4-[1-环己基-4-(4-氟苯基)-1H-咪唑-5-基]-2-嘧啶胺盐酸盐,PF 670462;PF670462) 目录号 : GC10556
An inhibitor of the CK1 isoforms CK1ε and CK1δ
Cas No.:950912-80-8
Sample solution is provided at 25 µL, 10mM.
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PF-670462 is a potent and selective inhibitor of CK1ε and CK1δ with IC50 value of 80 nM and 13 nM, respectively [1].
CK1ε and CK1δ belong to the casein kinase 1 family which is serine/threonine-selective enzyme and plays an important role in regulating circadian rhythm [1].
In COS-7 cells cotransfected with GFP-tagged PER3 and the human CK1ε enzyme, PF-670462 inhibited PER3 nuclear translocation in a concentration-dependent way [2]. In primary lung fibroblast cells obtained from WT mice, PF-670462 significantly lengthened the circadian period in a dose-dependent way. And with a dose of 1 μM, the period in WT fibroblast cells extended to 33 h [3].
In WT, Ck1ε−/− and Ck1εtau mice, PF-670462 (10 mg/kg/d) significantly lengthened the period of activity rhythms in all three genotypes (WT: 0.44 h, Ck1εtau: 0.39 h, Ck1ε−/−: 0.42 h). In WT mice, the activity onset occurred 10.4 h after 24 d of treatment. Also, PF-670462 caused identical period lengthening in WT and Ck1ε−/− mice, which suggested that the effect of CK1δ on the circadian period [3].
References:
[1]. Walton KM, Fisher K, Rubitski D, et al. Selective inhibition of casein kinase 1 epsilon minimally alters circadian clock period. J Pharmacol Exp Ther, 2009, 330(2): 430-439.
[2]. Badura L, Swanson T, Adamowicz W, et al. An inhibitor of casein kinase I epsilon induces phase delays in circadian rhythms under free-running and entrained conditions. J Pharmacol Exp Ther, 2007, 322(2): 730-738.
[3]. Meng QJ, Maywood ES, Bechtold DA, et al. Entrainment of disrupted circadian behavior through inhibition of casein kinase 1 (CK1) enzymes. Proc Natl Acad Sci U S A, 2010, 107(34): 15240-15245.
| Kinase experiment [1]: | |
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Kinase assays |
The CK1ε and CK1δ kinase assays were performed in a 20-μL volume in buffer containing 50 mM Tris, pH 7.5, 10 mM MgCl2, 1 mM DTT, 10 μM ATP and 42 μM peptide substrate (PLSRTLpSVASLPGL). The final enzyme concentrations were 2.5 nM for CK1ε and 2 nM for CK1δ. Assays were run in a panel format in the presence 1 μL of CK1 inhibitor or 5% DMSO. The reactions were incubated for 2 hrs at room temperature, followed by detection with 20 μL of the Kinase-Glo Plus Assay reagent. Luminescence was measured by using Enhanced Lum detection on an Envision plate reader. |
| Cell experiment [1]: | |
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Cell lines |
Rat1 cells |
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Preparation method |
The solubility of this compound in DMSO is > 20.5 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
0 ~ 50 μM |
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Applications |
In Rat1 cells, PF-670462 significantly lengthened the circadian period. At the concentration as low as 1 μM, PF-670462 started to dramatically increase the circadian period in a dose-dependent manner. PF-670462 began to increase the period of the clock at approximately 3- to 10-fold over the whole-cell CK1δ IC50 and approximately 3-fold lower for CK1ε. |
| Animal experiment [1]: | |
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Animal models |
C57BL/6J mice |
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Dosage form |
32 mg/kg; s.c.; a single dose |
|
Applications |
After a single subcutaneous dose of 32 mg/kg PF-670462, the brain-to-plasma concentration ratio of PF-670462 was constant throughout the 24-hr time course, with an average value of 1.3. The free brain Cmax of PF-670462 was 3-fold above its CK1δ whole-cell IC50, along with a 0.7-fold CK1ε whole-cell IC50, which indicated that PF-670462 inhibited most of the CK1δ and CK1ε activity. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Walton KM, Fisher K, Rubitski D, et al. Selective inhibition of casein kinase 1 epsilon minimally alters circadian clock period. J Pharmacol Exp Ther, 2009, 330(2): 430-439. | |
| Cas No. | 950912-80-8 | SDF | |
| 别名 | 4-[1-环己基-4-(4-氟苯基)-1H-咪唑-5-基]-2-嘧啶胺盐酸盐,PF 670462;PF670462 | ||
| 化学名 | 4-[3-cyclohexyl-5-(4-fluorophenyl)imidazol-4-yl]pyrimidin-2-amine;dihydrochloride | ||
| Canonical SMILES | C1CCC(CC1)N2C=NC(=C2C3=NC(=NC=C3)N)C4=CC=C(C=C4)F.Cl.Cl | ||
| 分子式 | C19H22Cl2FN5 | 分子量 | 410.32 |
| 溶解度 | ≥ 20.5 mg/mL in DMSO, ≥ 20.8 mg/mL in EtOH with ultrasonic and warming, ≥ 94 mg/mL in Water with ultrasonic and warming | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4371 mL | 12.1856 mL | 24.3712 mL |
| 5 mM | 0.4874 mL | 2.4371 mL | 4.8742 mL |
| 10 mM | 0.2437 mL | 1.2186 mL | 2.4371 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet