| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
The primary target of PF-4800567 hydrochloride is casein kinase 1 epsilon (CK1ε), a serine/threonine kinase that plays a critical role in the regulation of circadian rhythms and other cellular processes. PF-4800567 acts as a potent and selective ATP-competitive inhibitor of CK1ε with an IC50 of 32 nM. It exhibits 20-fold selectivity over CK1δ (IC50 = 711 nM). The compound is brain-penetrable, making it suitable for investigating CK1ε function in the central nervous system and its role in circadian rhythm regulation.
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|---|---|
| ln Vitro |
In vitro, PF-4800567 hydrochloride inhibits CK1ε kinase activity with an IC50 of 32 nM in biochemical assays. The compound demonstrates selectivity over CK1δ with an IC50 of 711 nM, representing approximately 20-fold selectivity. X-ray crystal structures of PF-4800567 bound to the kinase domains of human CK1ε and CK1δ have been determined, revealing the structural basis for its potency and selectivity. These in vitro activities confirm its utility as a pharmacological tool for investigating CK1ε function in cellular systems.
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| ln Vivo |
In vivo, PF-4800567 hydrochloride demonstrates brain penetration and has been used to investigate the role of CK1ε in circadian rhythm regulation. The compound exhibits dose-dependent effects on circadian period length in behavioral studies. Its ability to modulate circadian rhythms in vivo supports its utility as a research tool for studying the molecular mechanisms of circadian clock regulation and for investigating potential therapeutic applications in circadian rhythm disorders.
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| Enzyme Assay |
The in vitro enzyme assay for CK1ε inhibition involves the use of recombinant CK1ε enzyme and a synthetic peptide substrate. The kinase reaction is performed in a buffer containing HEPES, MgCl2, ATP, and DTT at physiological pH. PF-4800567 hydrochloride is incubated with the enzyme and substrate at 30°C for a defined period. The reaction is terminated by adding EDTA or a stop solution. Phosphorylated peptide substrate is detected using radiometric or fluorescence-based methods. IC50 values are calculated from dose-response curves generated with increasing compound concentrations.
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| Cell Assay |
The in vitro cell assay for PF-4800567 hydrochloride involves the culture of cells expressing CK1ε, such as HEK293 or NIH3T3 cells. Cells are treated with PF-4800567 hydrochloride at various concentrations. CK1ε activity is assessed by measuring phosphorylation of downstream substrates such as PER proteins by immunoblotting. Circadian rhythm assays are performed using luciferase reporter cell lines to monitor clock gene expression oscillations. Dose-response curves are generated to determine the cellular potency of CK1ε inhibition and its effects on circadian clock function.
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| Animal Protocol |
The in vivo animal experiment for PF-4800567 hydrochloride involves the use of rodents for circadian rhythm studies. Mice or rats receive PF-4800567 hydrochloride via oral gavage or intraperitoneal injection at various doses. Locomotor activity is monitored using running wheels or infrared activity sensors under constant darkness conditions. Circadian period length is determined by analyzing activity rhythms using actogram analysis. Brain tissue is harvested for pharmacokinetic analysis and assessment of CK1ε target engagement. Dose-response relationships are established to characterize the effects of CK1ε inhibition on circadian behavior.
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| References |
| Molecular Formula |
C17H19CL2N5O2
|
|---|---|
| Molecular Weight |
396.271061182022
|
| Exact Mass |
395.091
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| CAS # |
1391052-28-0
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| Related CAS # |
1188296-52-7;1391052-28-0 (HCl);
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| PubChem CID |
71751553
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
4
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| Heavy Atom Count |
26
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| Complexity |
439
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=CC(=C1)OCC2=NN(C3CCOCC3)C4=NC=NC(=C24)N)Cl.Cl
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| InChi Key |
QZXZQMUZEHTFHD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H18ClN5O2.ClH/c18-11-2-1-3-13(8-11)25-9-14-15-16(19)20-10-21-17(15)23(22-14)12-4-6-24-7-5-12;/h1-3,8,10,12H,4-7,9H2,(H2,19,20,21);1H
|
| Chemical Name |
3-[(3-chlorophenoxy)methyl]-1-(oxan-4-yl)pyrazolo[3,4-d]pyrimidin-4-amine;hydrochloride
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| HS Tariff Code |
2934.99.9001
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5235 mL | 12.6177 mL | 25.2353 mL | |
| 5 mM | 0.5047 mL | 2.5235 mL | 5.0471 mL | |
| 10 mM | 0.2524 mL | 1.2618 mL | 2.5235 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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