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| 25mg |
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Purity: ≥98%
PF-670462 (also known as PF670462; PF670) is a novel, potent and selective inhibitor of casein kinase (CK1ε and CK1δ) with anticancer activity. It inhibits CK1ε and CK1δ with IC50s of 7.7 nM and 14 nM, respectively. Casein kinase 1 delta and epsilon (CK1δ/ɛ) are key regulators of diverse cellular growth and survival processes including Wnt signaling, DNA repair and circadian rhythms. Recent studies suggest that they have an important role in oncogenesis. RNA interference screens identified CK1ɛ as a pro-survival factor in cancer cells in vitro and the CK1δ/ɛ-specific inhibitor IC261 is remarkably effective at selective, synthetic lethal killing of cancer cells.
| ln Vitro |
PF-670462, with an IC50 of 7.7 nM and 14 nM, respectively, is a strong and specific inhibitor of CKIε and CKIδ. With IC50s of 150 nM and 190 nM for EGFR and SAPK2A/p38, respectively, PF-670462 is less than a 30-fold selector for these two proteins. In CKIε-transfected COS7 cells, PF-670462 also redistributes the GFP signal to the cytoplasm in a concentration-dependent manner, with an EC50 of 290 ± 39 nM [1]. With an IC50 of about 17 nM, PF-670462 is a strong inhibitor of Wnt/β-catenin signaling. PF-670462 (1 μM) is a mild inhibitor of proliferation that only slightly impedes the growth of HT1080 and HEK293 cells. Strong inhibition of CK1ε and CK1δ is observed at 100 nM of PF-670462, which is in line with its actions on Wnt/β-catenin signaling [2].
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| ln Vivo |
In rats lacking exogenous time, PF-670462 (50 mg/kg, sc) induced a strong phase delay and demonstrated sustained activity without any discernible correction. A dose-dependent phase shift is induced by subcutaneous injection of PF-670462 at 25, 50, and 100 mg/kg [1]. The rhythmic transcription of Bmal1, Per1, Per2, and Nr1d1 in the liver and pancreas was considerably delayed by PF-670462 (50 mg/kg; sc) one day after administration, by 4.5 ± 1.3 hours and 4.5 ± 1.2 hours, respectively. The mRNA expression rhythms of Nr1d1 and Dbp are also 4.2 and 4 hours later, respectively, in the suprachiasmatic nucleus (SCN) [3].
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| References |
[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.
[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. [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 |
| Molecular Formula |
C19H22CL2FN5
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|---|---|
| Molecular Weight |
410.3159
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| CAS # |
950912-80-8
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| Related CAS # |
950980-98-0;950912-80-8 (HCl);
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| SMILES |
NC1=NC=CC(C2=C(C3=CC=C(F)C=C3)N=CN2C4CCCCC4)=N1.[H]Cl.[H]Cl
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| InChi Key |
PSNKGVAXBSAHCH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H20FN5.2ClH/c20-14-8-6-13(7-9-14)17-18(16-10-11-22-19(21)24-16)25(12-23-17)15-4-2-1-3-5-15;;/h6-12,15H,1-5H2,(H2,21,22,24);2*1H
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| Chemical Name |
4-[1-Cyclohexyl-4-(4-fluorophenyl)-1H-imidazol-5-yl]-2-pyrimidinamine dihydrochloride
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| Synonyms |
PF-670; PF-670462; PF670; PF 670462; PF 670; PF-670462 HCl; PF-670462 hydrochloride; PF670462.
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O : ~100 mg/mL (~243.71 mM)
DMSO : ≥ 32 mg/mL (~77.99 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.07 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.07 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: 25 mg/mL (60.93 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C). |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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