| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Human D1 Receptor 107 nM (EC50)
(Rac)-PF-06256142 is a D1 receptor agonist, but it is the less effective enantiomer compared to the (R)-form. It targets the dopamine D1 receptor (D1R), acting as an orthosteric agonist to activate Gs-mediated signaling. Its primary use is as a research control to compare against the more potent enantiomer. |
|---|---|
| ln Vitro |
In vitro, (Rac)-PF-06256142 is a D1 receptor agonist with an EC50 of 107 nM. This is significantly less potent than the (R)-enantiomer of PF-06256142, which has an EC50 of 33 nM and a Ki of 12 nM for the D1 receptor. This marked difference in potency defines its role as a control compound.
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| ln Vivo |
No specific in vivo data is provided for the racemic mixture. For the active (R)-enantiomer, in vivo activity includes being orally active and CNS-penetrant, making it useful for research into neurological disorders like Parkinson‘s disease and schizophrenia. (Rac)-PF-06256142 is not intended for primary in vivo use due to its lower potency.
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| Enzyme Assay |
The non-cellular binding affinity is typically determined by a radioligand competition assay using human D1 receptor membranes. Membranes are incubated with [3H]SCH23390 (a D1 antagonist) and increasing concentrations of (Rac)-PF-06256142 or its (R)-enantiomer for comparison. Bound radioactivity is measured after filtration, and Ki values are calculated.
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| Cell Assay |
A functional cellular assay for the racemate uses a HEK-293 cell line stably expressing the human D1 receptor and a CRE-luciferase reporter. Cells are exposed to increasing concentrations of (Rac)-PF-06256142, and the D1 agonist activity is measured as an increase in luminescence, which is directly proportional to intracellular cAMP levels induced by Gs pathway activation.
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| Animal Protocol |
No in vivo protocol for (Rac)-PF-06256142 is provided, as it is a control compound. For the active (R)-enantiomer, in vivo studies typically involve oral administration to rodent models of Parkinson's disease, followed by behavioral tests (e.g., locomotor activity, forelimb use) to assess reversal of motor deficits.
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| ADME/Pharmacokinetics |
No specific PK data for (Rac)-PF-06256142 is provided. As the less active enantiomer, it is not typically advanced for in vivo pharmacokinetic characterization. The active (R)-enantiomer is known to be CNS-penetrant and orally active, suggesting it has favorable ADME properties.
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| Toxicity/Toxicokinetics |
No specific toxicological data is provided for (Rac)-PF-06256142. As an inactive control, toxicity is not the primary focus. The active (R)-enantiomer is designed to have an improved safety profile with reduced receptor desensitization relative to dopamine, which may lower the risk of dyskinesia seen with non-selective agonists.
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| References |
[1]. Davoren JE, et al. Discovery and Lead Optimization of Atropisomer D1 Agonists with Reduced Desensitization. J Med Chem. 2018 Nov 15.
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| Additional Infomation |
(Rac)-PF-06256142 is a critical negative control tool for researchers investigating the pharmacology of the potent D1 agonist PF-06256142. Its significantly lower potency confirms that biological effects observed with the active enantiomer are likely mediated by the D1 receptor and not due to non-target interactions or vehicle effects, validating the specificity of the D1 activation model.
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| Molecular Formula |
C21H16N4O2
|
|---|---|
| Molecular Weight |
356.3773
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| Exact Mass |
356.127
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| CAS # |
1609580-97-3
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| Related CAS # |
PF-06256142;1609583-14-3;(R)-PF-06256142;1609583-15-4
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| PubChem CID |
75201901
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
4.3
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| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
3
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| Heavy Atom Count |
27
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| Complexity |
520
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(C=CC(=C1)OC2=NC=CC3=C2C=CO3)C4=C(N=CC5=NC=CN54)C
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| InChi Key |
HWAIAGZSWHOLLK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H16N4O2/c1-13-11-15(27-21-17-6-10-26-18(17)5-7-23-21)3-4-16(13)20-14(2)24-12-19-22-8-9-25(19)20/h3-12H,1-2H3
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| Chemical Name |
4-[3-methyl-4-(6-methylimidazo[1,2-a]pyrazin-5-yl)phenoxy]furo[3,2-c]pyridine
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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) |
DMSO: 25 mg/mL (70.15 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.01 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 25.0 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: ≥ 2.5 mg/mL (7.01 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 25.0 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: ≥ 2.5 mg/mL (7.01 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8060 mL | 14.0300 mL | 28.0599 mL | |
| 5 mM | 0.5612 mL | 2.8060 mL | 5.6120 mL | |
| 10 mM | 0.2806 mL | 1.4030 mL | 2.8060 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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