الصفحة الرئيسية>>Signaling Pathways>> DNA Damage/DNA Repair>> Casein Kinase>>PF-670462

PF-670462

رقم الكتالوجGC10556

An inhibitor of the CK1 isoforms CK1ε and CK1δ

Products are for research use only. Not for human use. We do not sell to patients.

PF-670462 التركيب الكيميائي

Cas No.: 950912-80-8

الحجم السعر المخزون الكميّة
10mM (in 1mL DMSO)
109٫00
متوفر
10mg
87٫00
متوفر
50mg
385٫00
متوفر
500mg
1700٫00
متوفر
1g
2554٫00
متوفر

Tel:(909) 407-4943 Email: sales@glpbio.com


مراجعات العميل

بناء على آراء العملاء.

  • GlpBio Citations

    GlpBio Citations
  • Bioactive Compounds Premium Provider

    Bioactive Compounds Premium Provider

Sample solution is provided at 25 µL, 10mM.

Description of PF-670462

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.

Protocol of PF-670462

Kinase experiment [1]:

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]:

Cell lines

Rat1 cells

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.

Reacting condition

0 ~ 50 μM

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]:

Animal models

C57BL/6J mice

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.

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.

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.

Chemical Properties of PF-670462

Cas No. 950912-80-8 SDF
Chemical Name 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
Formula C19H22Cl2FN5 M.Wt 410.32
الذوبان ≥ 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 Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table of PF-670462

Prepare stock solution
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
  • حاسبة المولارية

  • حاسبة التخفيف

  • Molecular Weight Calculator

كتلة
=
تركيز
x
مقدار
x
ميغاواط *
 
 
 
** عند إعداد حلول المخزون، دائمًا استخدم الوزن الجزيئي الخاص بالدفعة للمنتج على ملصق القارورة MSDS / CoA (متوفر عبر الإنترنت).

احسب

In vivo Formulation Calculator (Clear solution) of PF-670462

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.

Product Documents

Quality Control & SDS

View current batch:

مراجعات

Review for PF-670462

Average Rating: 5 ★★★★★ (Based on Reviews and 30 reference(s) in Google Scholar.)

5 Star
100%
4 Star
0%
3 Star
0%
2 Star
0%
1 Star
0%
Review for PF-670462

GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.

Required fields are marked with *

You may receive emails regarding this submission. Any emails will include the ability to opt-out of future communications.