| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
Ki: 9.4 nM (GPR6)[1] EC50: 38 nM (GPR6)[1]
Targets GPR6, a constitutively active orphan GPCR that is highly expressed in the striatum, a brain region critical for motor control and reward. CVN424 acts as an inverse agonist (EC50 = 38 nM, Ki = 9.4 nM), meaning it not only blocks agonist-driven activity but also actively reduces the receptor's baseline, constitutive level of activity, which is a key feature of GPR6. |
|---|---|
| ln Vitro |
The selectivity of CVN424 (compound 6i) for GPR3 and GPR12 is 265-fold and 68-fold, respectively [1].
As an inverse agonist, CVN424 binds to GPR6 and stabilizes its inactive state, reducing the receptor‘s high baseline activity. By inhibiting GPR6 signaling, it effectively modulates downstream pathways, including the cAMP signaling cascade. It has been shown to be highly selective for GPR6, with no significant activity at related GPCRs like GPR3 or GPR12. |
| ln Vivo |
CVN424 has shown efficacy in preclinical models of Parkinson‘s disease. Oral administration of CVN424 dose-dependently increases locomotor activity and reverses haloperidol-induced catalepsy, a standard preclinical model used to predict anti-parkinsonian activity. It is brain-penetrant and shows dose-dependent receptor occupancy in the brain.
|
| Enzyme Assay |
CVN424 is a highly specific GPR6 inverse agonist. No non-cell assay data is required for its description as an inverse agonist. Its binding affinity (Ki = 9.4 nM) is determined through standard GPCR radioligand binding assays, while its inverse agonism is characterized using functional assays measuring its ability to reduce constitutive receptor activity.
|
| Cell Assay |
Functional cellular assays for CVN424 are used to confirm inverse agonism. Cells expressing GPR6, which has high constitutive activity, are treated with the compound. The ability of CVN424 to reduce this baseline activity, typically by measuring its effect on intracellular cAMP levels, is quantified. The EC50 of 38 nM is the concentration required to produce 50% of this maximal inhibitory effect.
|
| Animal Protocol |
In the haloperidol-induced catalepsy model, rats are treated with haloperidol to induce a cataleptic state (rigidity and immobility). CVN424 is then administered orally. The reversal of catalepsy is measured at various time points using a standard bar test, where the time the animal remains immobile is recorded. Increased locomotor activity is also measured using an open field test.
|
| ADME/Pharmacokinetics |
CVN424 is orally active and brain-penetrant, demonstrating the required pharmacokinetic properties for a CNS drug. In mice and rats, a brain receptor occupancy of 50% is achieved at plasma concentrations of 6.0 ng/ml and 7.4 ng/ml, respectively. Detailed human PK data from its clinical trials is available but not public.
|
| Toxicity/Toxicokinetics |
Detailed toxicity data from its clinical trials is not fully public. As a drug candidate in development, CVN424 has likely passed standard preclinical toxicology studies. In published preclinical studies, no overt toxicities are mentioned at the doses tested. Clinical trial data reports the drug is generally safe and well-tolerated, with mild-to-moderate side effects.
|
| References |
|
| Additional Infomation |
CVN-424 is being studied in the clinical trial NCT06006247 (CVN424 monotherapy for early-stage Parkinson's disease).
CVN424 is an investigational drug that has successfully completed Phase 1 and Phase 2 clinical trials for Parkinson‘s disease. It is not yet approved by the FDA. It represents a novel, first-in-class approach to treating Parkinson‘s by targeting the GPR6 receptor, a novel non-dopaminergic pathway, offering a potential alternative to standard dopamine-based therapies. |
| Molecular Formula |
C24H29F2N5O3
|
|---|---|
| Molecular Weight |
473.5156
|
| Exact Mass |
473.223
|
| CAS # |
2254706-21-1
|
| PubChem CID |
137359492
|
| Appearance |
Light yellow to green yellow solid powder
|
| LogP |
2.4
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
34
|
| Complexity |
698
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
FC1C([H])=C(C([H])=C([H])C=1OC1([H])C([H])([H])C([H])([H])N(C2C(=NC3C([H])([H])N(C(C([H])([H])[H])=O)C([H])([H])C([H])([H])C=3N=2)N([H])[C@@]2([H])C([H])([H])OC([H])([H])C2([H])[H])C([H])([H])C1([H])[H])F
|
| InChi Key |
HSWVJQBEXRKOBZ-QGZVFWFLSA-N
|
| InChi Code |
InChI=1S/C24H29F2N5O3/c1-15(32)31-10-6-20-21(13-31)28-23(27-17-7-11-33-14-17)24(29-20)30-8-4-18(5-9-30)34-22-3-2-16(25)12-19(22)26/h2-3,12,17-18H,4-11,13-14H2,1H3,(H,27,28)/t17-/m1/s1
|
| Chemical Name |
1-[2-[4-(2,4-difluorophenoxy)piperidin-1-yl]-3-[[(3R)-oxolan-3-yl]amino]-7,8-dihydro-5H-pyrido[3,4-b]pyrazin-6-yl]ethanone
|
| 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: 62.5 mg/mL (131.99 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.39 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 (4.39 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: ≥ 2.08 mg/mL (4.39 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 | 2.1118 mL | 10.5592 mL | 21.1184 mL | |
| 5 mM | 0.4224 mL | 2.1118 mL | 4.2237 mL | |
| 10 mM | 0.2112 mL | 1.0559 mL | 2.1118 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.
Link: https://clinicaltrials.gov/ct2/show/NCT06553027
Conditions:Parkinson DiseaseLink: https://clinicaltrials.gov/ct2/show/NCT06006247
Conditions:Parkinson's DiseaseLink: https://clinicaltrials.gov/ct2/show/NCT05635461
Conditions:Parkinson's Disease
Title:Study of CVN424 in Parkinson's Disease Patients With Motor Fluctuations
Status:Completed
updateDate:2024-07-03
Ctid:NCT04191577
Link: https://clinicaltrials.gov/ct2/show/NCT04191577
Conditions:Parkinson DiseaseLink: https://clinicaltrials.gov/ct2/show/NCT03657030
Conditions:HealthyProducts are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
