| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| Other Sizes |
| Targets |
D1 Receptor
The primary target of (Rac)-Tavapadon is the dopamine D1 receptor (D1R). It acts as a non-catechol agonist, displaying potent full agonism in Gs-mediated cAMP accumulation assays and partial agonism in beta-arrestin2 recruitment assays, indicating functional selectivity (biased agonism) at the D1 receptor. |
|---|---|
| ln Vitro |
Compound 32; (Rac)-Tavapadon ((Rac)-PF-06649751) has EMAXs in the β-arrestin2 recruitment assay and the GS activation assay of 118% and 30%, respectively[1].
In vitro, (Rac)-Tavapadon acts as a potent full agonist in the Gs activation assay, stimulating cAMP accumulation with an EC50 of 0.8 nM. In the same system, it acts as a partial agonist in the beta-arrestin2 recruitment assay, with an EC50 of 68 nM. This functional selectivity distinguishes it from catechol-based D1 agonists. |
| ln Vivo |
Specific in vivo data for (Rac)-Tavapadon is not detailed. However, the active enantiomer of this mixture has demonstrated anti-Parkinson's activity in animal models. In rodent models of Parkinson's disease, Tavapadon has been shown to reverse motor deficits by selectively activating D1 receptors in the striatum, without the desensitization or dyskinesia associated with non-selective dopaminergic therapies.
|
| Enzyme Assay |
A typical non-cellular assay for D1 receptor binding uses radioligand competition. Membrane preparations from HEK-293 cells expressing the human D1 receptor are incubated with [3H]SCH23390 and varying concentrations of (Rac)-Tavapadon in 50 mM Tris-HCl buffer (pH 7.4) for 60 min at room temperature. Nonspecific binding is determined with 10 uM butaclamol.
|
| Cell Assay |
For functional assays, HEK-293 cells co-expressing the human D1 receptor and a CRE-luciferase reporter are used. Cells are seeded, treated with increasing concentrations of (Rac)-Tavapadon (10 pM to 10 uM) in the presence of forskolin, and incubated for 5 h at 37degC. Luciferase activity is measured to determine the EC50 for Gs pathway activation.
|
| Animal Protocol |
No specific in vivo protocol is provided. For standard efficacy studies, a rat model of Parkinson's disease (e.g., 6-OHDA lesion) is used. (Rac)-Tavapadon is administered via subcutaneous injection, and motor deficits are assessed using the forelimb adjusting steps test or amphetamine-induced rotation to evaluate the reversal of akinesia and motor asymmetry.
|
| ADME/Pharmacokinetics |
No specific PK data is provided for the racemate. However, the active enantiomer is known to be orally bioavailable and CNS-penetrant. For a dopamine D1 agonist, typical PK parameters of interest would include its half-life (t1/2), brain-to-plasma ratio, and oral bioavailability to ensure sufficient central exposure for motor effects.
|
| Toxicity/Toxicokinetics |
No specific toxicological data is provided for (Rac)-Tavapadon. Dopamine D1 agonists, if not selective, can cause hypotension, nausea, and dyskinesia. The functional selectivity of this compound is designed to minimize such side effects, but detailed safety studies are not provided for this racemic research mixture.
|
| References | |
| Additional Infomation |
Tavapadon is currently being investigated in the clinical trial NCT02262767 (a study of the safety, tolerability, and pharmacokinetics of PF-06649751 in combination with trimetobenzamide hydrochloride in healthy subjects).
Drug Indication Treatment of Parkinson's Disease (Rac)-Tavapadon is a racemate of Tavapadon (PF-06649751), which has been in clinical development for Parkinson‘s disease. Its mechanism of action involves bias signaling, preferring the Gs pathway over beta-arrestin2 recruitment, which is hypothesized to reduce motor complications like dyskinesia associated with long-term levodopa therapy, representing a novel strategy for symptomatic treatment. |
| Molecular Formula |
C19H16F3N3O3
|
|---|---|
| Molecular Weight |
391.343854904175
|
| Exact Mass |
391.114
|
| CAS # |
1643462-64-9
|
| Related CAS # |
Tavapadon;1643489-24-0
|
| PubChem CID |
86764100
|
| Appearance |
White to off-white solid powder
|
| LogP |
3.3
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
28
|
| Complexity |
665
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1(=O)N(C)C(C2=CC=C(OC3=NC=CC=C3C(F)(F)F)C=C2C)=C(C)C(=O)N1
|
| InChi Key |
AKQXQLUNFKDZBN-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C19H16F3N3O3/c1-10-9-12(28-17-14(19(20,21)22)5-4-8-23-17)6-7-13(10)15-11(2)16(26)24-18(27)25(15)3/h4-9H,1-3H3,(H,24,26,27)
|
| Chemical Name |
1,5-dimethyl-6-[2-methyl-4-[3-(trifluoromethyl)pyridin-2-yl]oxyphenyl]pyrimidine-2,4-dione
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO: 41.67 mg/mL (106.48 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 4.17 mg/mL (10.66 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 41.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5553 mL | 12.7766 mL | 25.5532 mL | |
| 5 mM | 0.5111 mL | 2.5553 mL | 5.1106 mL | |
| 10 mM | 0.2555 mL | 1.2777 mL | 2.5553 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
