PF-670462 dihydrochloride
Based on 8 publication(s) in Google Scholar
PF-670462 dihydrochloride is a potent and selective inhibitor of casein kinase (CK1ε and CK1δ), with IC50s of 7.7 nM and 14 nM, respectively.
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza: 99.96%
- No. CAS: 950912-80-8
- Fòrmula: C19H22Cl2FN5
- Peso molecular:410.32
-
Almacenamiento:
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Actividad biológica
-
Chemical Information
-
Solvente y solubilidad
- Protocolo
- Pureza y Documentación
- Referencias
-
Help & FAQs
-
Bioactive Compound Library Max
HY-L181
-
Bioactive Compound Library
HY-L001
-
Cell Cycle/DNA Damage Compound Library
HY-L004
-
Kinase Inhibitor Library
HY-L009
-
Stem Cell Signaling Compound Library
HY-L017
-
Wnt/Hedgehog/Notch Compound Library
HY-L020
-
Anti-Cancer Compound Library
HY-L025
-
Anti-Aging Compound Library
HY-L034
-
Cancer Stem Cells Compound Library
HY-L135
-
Highly Selective Inhibitors Library
HY-L158
-
Serine/Threonine Kinase Inhibitor Library
HY-L164
-
Multi-Target Compound Library
HY-L176
-
MCE Bioactive Compound Library
HY-L001V
-
Protein Kinase Compound Library
HY-L196
-
High-Throughput Bioactive Compound Library
HY-L205
-
Posttranslational Modification Library
HY-L226
Publications Citing Use of MedChemExpress (MCE) PF-670462 dihydrochloride
More- Sci Transl Med. 2018 Jul 18;10(450):eaaq1093. [Abstract]
- Proc Natl Acad Sci U S A. 2024 Jul 16;121(29):e2321647121. [Abstract]
- Proc Natl Acad Sci U S A. 2018 Aug 7;115(32):E7522-E7531. [Abstract]
- Antioxidants (Basel). 2021 Nov 26;10(12):1898. [Abstract]
- EMBO Rep. 2021 Jul 5;22(7):e51847. [Abstract]
- Biochem Biophys Res Commun. 2020 Mar 12;523(3):809-815. [Abstract]
- bioRxiv. 2025 January 15.
- J Pers Med. 2021 Sep 11;11(9):906. [Abstract]
Customer Validation & Images
-
WB
-
Cell Imaging/Staining
-
WB
-
WB
-
WB
Actividad biológica
|
CK1δ 14 nM (IC50) |
EGFR 150 nM (IC50) |
SAPK2A/p38 190 nM (IC50) |
PF-670462 is a potent and selective inhibitor of CKIε and CKIδ, with IC50s of 7.7 nM and 14 nM, respectively. PF-670462 shows less than 30-fold selevtivity for EGFR and SAPK2A/p38, with IC50s of 150 nM and 190 nM, respectively. PF-670462 also causes a redistribution of the GFP signal to the cytoplasm in a concentration-dependent manner, with an EC50 of 290 ± 39 nM in CKIε-transfected COS7 cells[1].
PF-670462 is a potent inhibitor of Wnt/β-catenin signaling, with an IC50 of ～17?nM. PF-670462 (1?μM) is a weak inhibitor of proliferation, and only modestly suppresses the growth of HEK293 and HT1080 cells. PF-670462 (100 nM) strongly inhibits CK1ε and CK1δ, consistent with its effect on Wnt/β-catenin signaling[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
-
No. CAS 950912-80-8
-
Appearance Solid
-
Peso molecular 410.32
-
Fòrmula C19H22Cl2FN5
-
Color White to yellow
-
SMILES
NC1=NC=CC(C2=C(C3=CC=C(F)C=C3)N=CN2C4CCCCC4)=N1.[H]Cl.[H]Cl
-
Envío
Room temperature in continental US; may vary elsewhere.
-
Almacenamiento
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Publications (8)
-
Journal Impact Factor
-
Most Recent
-
Sci Transl Med
PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells. [Abstract]2018 Jul 18;10(450):eaaq1093. PMID: 30021885 -
Proc Natl Acad Sci U S A
FAM110A promotes mitotic spindle formation by linking microtubules with actin cytoskeleton. [Abstract]2024 Jul 16;121(29):e2321647121. PMID: 38995965
PF-670462 dihydrochloride purchased from MedChemExpress. Usage Cited in: Proc Natl Acad Sci U S A. 2024 Jul 16;121(29):e2321647121. [Abstract]
HEK293 cells transfected with indicated constructs were arrested in mitosis with NDZ and treated or not with PF-670462 dihydrochloride (1 µM) for 6 h. Pull-down from cell extracts was performed using GFP-Trap, and binding of tubulin and actin was determined by immunoblotting (n = 2).
PF-670462 dihydrochloride purchased from MedChemExpress. Usage Cited in: Proc Natl Acad Sci U S A. 2024 Jul 16;121(29):e2321647121. [Abstract]
Representative live image sequence of RPE-sAC-GFP cells treated with DMSO or with CK1 inhibitor PF-670462 dihydrochloride (1 µM; 15 min). Cells were imaged every 25 s, time 0 was set to indicate NEB. The results showed that inhibition of CK1 by PF-670462 dihydrochloride impaired organization of the spindle actin in prophase cells. (Scale bar, 10 μm.)
-
Proc Natl Acad Sci U S A
Tumor promoter TPA activates Wnt/β-catenin signaling in a casein kinase 1-dependent manner. [Abstract]2018 Aug 7;115(32):E7522-E7531. PMID: 30038030
PF-670462 dihydrochloride purchased from MedChemExpress. Usage Cited in: Proc Natl Acad Sci U S A. 2018 Aug 7;115(32):E7522-E7531. [Abstract]
The recombinant CK1ε phosphorylates Thr1479 of GST-LRP6 mini fragment in vitro, and TPA enhances CK1ε kinase activity. GST-LRP6 mini fragment fusion protein was incubated with recombinant CK1ε in the presence of 200 μM ATP with or without 160 μM TPA or 2 μM PF-670462 dihydrochloride as indicated. The detection of the phosphorylation of Thr1479 was performed by immunoblotting using an anti–phospho-LRP6 (Thr1479) antibody. Thr1479 phosphorylation levels were quantitated by densitometry and normalized to GST-LRP6 mini levels. Quantitated results are displayed (Right). The results showed that PF670462 (specific CK1 inhibitor) markedly suppresses CK1ε-triggered LRP6 phosphorylation at Thr1479. Phosphorylation of Thr1479 is indicated by an asterisk.
PF-670462 dihydrochloride purchased from MedChemExpress. Usage Cited in: Proc Natl Acad Sci U S A. 2018 Aug 7;115(32):E7522-E7531. [Abstract]
TPA rescued the inhibitory effect of PF-670462 dihydrochloride on the kinase activity of CK1ε. The GST-LRP6 mini fusion protein was incubated with CK1ε in the absence or presence of 2 μM PF-670462 dihydrochloride or the indicated amounts of TPA. Thr1479 phosphorylation of GST-LRP6 mini was measured by immunoblotting using anti–phospho-LRP6 (Thr1479) antibody, indicated by p-LRP6 (Thr1479). Phosphorylation of Thr1479 is indicated by an asterisk.
-
Antioxidants (Basel)
2021 Nov 26;10(12):1898. PMID: 34942999 -
EMBO Rep
CK1-mediated phosphorylation of FAM110A promotes its interaction with mitotic spindle and controls chromosomal alignment. [Abstract]2021 Jul 5;22(7):e51847. PMID: 34080749 -
Biochem Biophys Res Commun
IC261 suppresses progression of hepatocellular carcinoma in a casein kinase 1 δ/ε independent manner. [Abstract]2020 Mar 12;523(3):809-815. PMID: 31954519
PF-670462 dihydrochloride purchased from MedChemExpress. Usage Cited in: Biochem Biophys Res Commun. 2020 Mar 12;523(3):809-815. [Abstract]
Immunoblot analysis of cells treated with IC261 or PF-670462 dihydrochloride for 48 h. GAPDH served as a loading control.
-
-
J Pers Med
GPR30 Activation by 17β-Estradiol Promotes p62 Phosphorylation and Increases Estrogen Receptor α Protein Expression by Inducing Its Release from a Complex Formed with KEAP1. [Abstract]2021 Sep 11;11(9):906. PMID: 34575683
Solvente y solubilidad
H2O : 100 mg/mL (243.71 mM; Need ultrasonic)
DMSO : ≥ 32 mg/mL (77.99 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.08 mg/mL (5.07 mM); Clear solution
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.08 mg/mL (5.07 mM); Clear solution
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
For the following dissolution methods, please prepare the working solution directly:
It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: PBS
Solubility: 25 mg/mL (60.93 mM); Clear solution; Need ultrasonic and warming and heat to 60°C
Please enter the basic information of animal experiments:
-
-
-
-
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Working solution concentration: 0.22 mg/mL
This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.
Protocolo
The CKIε kinase assay is performed in a 40-μL final volume in buffer containing 50 mM Tris, pH 7.5, 10 mM MgCl2, 5 mM dithiothreitol with 5 μM ATP, 3 nM CKIεΔ319, and 15 μM peptide substrate PLSRTLpSVASLPGL in the presence of 5 μL of CKIε inhibitor (PF-670462) or 5% dimethyl sulfoxide. The reaction is incubated for 3 h at 27°C; detection is carried out as described for the Kinase-Glo Assay. Luminescent output is measured[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Adult male CD rats (initial weight 175-225 g) are released into constant darkness (DD) for 2 weeks, and their individual free-running periods and times of activity onset are determined from the 7 to 10 days at the end of the 2-week period. Dosing of 50 mg/kg PF-670462 or vehicle (40% β-cyclodextrin) takes place at circadian time (CT)9 or 3 h before the predicted onset of activity; night vision goggles facilitated the subcutaneous administration. CT9 is chosen based on preliminary data demonstrating robust responses to CKIε inhibition at this circadian time. Animals are maintained under DD for an additional 4 to 5 days postdose, and the data from that time period are used in the estimation of the magnitude and direction of the putative phase shifts[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Pureza y Documentación
-
Ficha de datos (288 KB)
-
SDS (394 KB)
- English - EN (394 KB)
- Français - FR (394 KB)
- Deutsch - DE (394 KB)
- Norwegian - NO (394 KB)
- Español - ES (394 KB)
- Swedish - SV (394 KB)
- Italian - IT (394 KB)
- Korean - KR (394 KB)
- Portuguese - PT (394 KB)
-
Instrucciones de manejo (2659 KB)
Referencias
[1]. Badura L, 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 Aug;322(2):730-8. Epub 2007 May 14. [Content Brief]
[2]. Cheong JK, et al. IC261 induces cell cycle arrest and apoptosis of human cancer cells via CK1δ/? and Wnt/β-catenin independent inhibition of mitotic spindle formation. Oncogene. 2011 Jun 2;30(22):2558-69. [Content Brief]
[3]. Kennaway DJ, et al. Acute inhibition of casein kinase 1δ/ε rapidly delays peripheral clock gene rhythms. Mol Cell Biochem. 2015 Jan;398(1-2):195-206. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO / H2O | 1 mM | 2.4371 mL | 12.1856 mL | 24.3712 mL | 60.9281 mL |
| 5 mM | 0.4874 mL | 2.4371 mL | 4.8742 mL | 12.1856 mL | |
| 10 mM | 0.2437 mL | 1.2186 mL | 2.4371 mL | 6.0928 mL | |
| 15 mM | 0.1625 mL | 0.8124 mL | 1.6247 mL | 4.0619 mL | |
| 20 mM | 0.1219 mL | 0.6093 mL | 1.2186 mL | 3.0464 mL | |
| 25 mM | 0.0975 mL | 0.4874 mL | 0.9748 mL | 2.4371 mL | |
| 30 mM | 0.0812 mL | 0.4062 mL | 0.8124 mL | 2.0309 mL | |
| 40 mM | 0.0609 mL | 0.3046 mL | 0.6093 mL | 1.5232 mL | |
| 50 mM | 0.0487 mL | 0.2437 mL | 0.4874 mL | 1.2186 mL | |
| 60 mM | 0.0406 mL | 0.2031 mL | 0.4062 mL | 1.0155 mL | |
| H2O | 80 mM | 0.0305 mL | 0.1523 mL | 0.3046 mL | 0.7616 mL |
| 100 mM | 0.0244 mL | 0.1219 mL | 0.2437 mL | 0.6093 mL |
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
PF-670462 dihydrochloride Related Classifications
HY-15490 Related Classifications
Powered by Bioz