Alofropodect
Alofropodect is an orally active, blood-brain barrier permeable phosphodiesterase 10A (PDE10A) inhibitor with IC50 values of 1 nM (Reference 1) and 35 nM (Reference 2). Alofropodect acts as a negative allosteric modulator of the M2 muscarinic receptor with an IC50 of 9.2 μM. Alofropodect alters cyclic nucleotide levels in basal ganglia circuits, inhibits the hydrolysis of cAMP and cGMP, and suppresses hERG potassium channel tail currents. Alofropodect induces catalepsy in rats and reverses injury-induced contralateral forelimb use impairment. Alofropodect can be used in research related to schizophrenia, Parkinson's disease, and levodopa-induced dyskinesia.
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- CAS No.: 1829530-11-1
- Formule: C19H15N7
- Masse moléculaire:341.37
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
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Solvant et solubilité
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
Description
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PDE10A 1 nM (IC50) |
PDE10A 35 nM (IC50) |
In Vitro
Alofropodect (0.1-10 μM; 5 min) inhibits hERG tail current in hERG-HEK-293 transfected cells with an IC25 of 3.2 μM[1].
Alofropodect (0.0457-100 μM; 14 days) does not affect key cardiac spheroid health parameters up to 100 μM, but impairs DNA structure with an IC50 of 37.4 μM in human pluripotent cell-derived 3D cardiac spheroids[1].
Alofropodect (8 nM-60 μM; 72 h) is not cytotoxic at concentrations up to 60 μM in NCI-H1299, HepG2, and SH-SY5Y cell lines[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Parmacokinetics
In Vivo
Alofropodect (0.1-0.3 mg/kg; p.o.; single acute administration combined with Levodopa (HY-N0304)/Benserazide (HY-121275) for 16 consecutive days) dose-dependently improves sensorimotor deficits in 6-hydroxydopamine-lesioned rats[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague-Dawley (male, ~300 g)[1]
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Dosage:0.15 mg/kg; 0.3 mg/kg; 0.6 mg/kg; 2 mg/kg
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Administration:p.o.; single dose
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Result:Did not induce catalepsy at 0.15 mg/kg.
Induced a low cataleptogenic effect only at 210 min and 240 min post-administration at 0.3 mg/kg.
Induced catalepsy from 120 min to 240 min post-administration at 0.6 mg/kg, with effect less than positive control haloperidol.
Produced a strong cataleptogenic effect comparable to haloperidol at 2 mg/kg.
Confirmed minimum effective dose (MED) for catalepsy as 0.6 mg/kg via AUC data.
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Animal Model:Wistar Han (male, initial body weight 270-300 g, unilateral medial forebrain bundle lesion with 6-hydroxydopamine)[2]
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Dosage:0.1 mg/kg (acute single dose; chronic daily combined with L-DOPA/benserazide); 0.3 mg/kg (acute single dose; chronic daily combined with L-DOPA/benserazide)
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Administration:p.o.; single acute dose; daily for 16 days (combined with L-DOPA/benserazide)
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Result:Dose-dependently reversed impaired forelimb use in the stepping test after acute administration.
Completely restored forelimb use symmetry in the cylinder test during the second post-dose testing session at 0.3 mg/kg acute dose.
Did not affect vibrissae test deficits or lesion-induced catalepsy at either acute dose.
Significantly improved impaired forelimb performance in the vibrissae test when combined acutely with L-DOPA at 0.1 mg/kg.
Reduced L-DOPA-induced contralateral rotations when combined acutely with L-DOPA at 0.3 mg/kg.
Completely reversed forelimb asymmetry in the vibrissae test after chronic combined treatment at 0.3 mg/kg.
Did not alter L-DOPA's antiparkinsonian effects in the stepping, catalepsy, or rotation tests at either chronic dose.
Significantly improved impaired forelimb use in the stepping test in the OFF phase post-chronic treatment at 0.3 mg/kg combined with L-DOPA compared to lesioned rats.
Chemical Information
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CAS No. 1829530-11-1
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Masse moléculaire 341.37
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Formule C19H15N7
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SMILES
CC1=NC=C(C)N2N=C(C3=NC4=NC(C5=CC=CC=C5)=CN4C=C3)N=C21
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Synonyms
CPL500036
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Solvant et solubilité
In Vitro:
DMSO : 25 mg/mL (73.23 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (7.32 mM); Suspended solution
This protocol yields a suspended solution of ≥ 2.5 mg/mL (saturation unknown). Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureté et documentation
Références
[1]. Matloka M, et al. A PDE10A inhibitor CPL500036 is a novel agent modulating striatal function devoid of most neuroleptic side-effects. Front Pharmacol. 2022;13:999685. Published 2022 Nov 9. [Content Brief]
[2]. Lenda T, et al. Antiparkinsonian-like effects of CPL500036, a novel selective inhibitor of phosphodiesterase 10A, in the unilateral rat model of Parkinson's disease. Eur J Pharmacol. 2021;910:174460. [Content Brief]
Complete Stock Solution Preparation Table
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| DMSO | 1 mM | 2.9294 mL | 14.6469 mL | 29.2937 mL | 73.2343 mL |
| 5 mM | 0.5859 mL | 2.9294 mL | 5.8587 mL | 14.6469 mL | |
| 10 mM | 0.2929 mL | 1.4647 mL | 2.9294 mL | 7.3234 mL | |
| 15 mM | 0.1953 mL | 0.9765 mL | 1.9529 mL | 4.8823 mL | |
| 20 mM | 0.1465 mL | 0.7323 mL | 1.4647 mL | 3.6617 mL | |
| 25 mM | 0.1172 mL | 0.5859 mL | 1.1717 mL | 2.9294 mL | |
| 30 mM | 0.0976 mL | 0.4882 mL | 0.9765 mL | 2.4411 mL | |
| 40 mM | 0.0732 mL | 0.3662 mL | 0.7323 mL | 1.8309 mL | |
| 50 mM | 0.0586 mL | 0.2929 mL | 0.5859 mL | 1.4647 mL | |
| 60 mM | 0.0488 mL | 0.2441 mL | 0.4882 mL | 1.2206 mL |
Alofropodect Related Classifications
HY-182638 Related Classifications
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