| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Targets |
PD-144418 targets the sigma 1 (σ1) receptor, a unique intracellular chaperone protein involved in cellular stress responses, calcium signaling, and modulation of ion channel activity. The compound has a Ki of 0.08 nM for σ1 and 1377 nM for σ2 receptors, demonstrating >3000-fold selectivity. It shows no significant affinity for a wide range of other receptors, ion channels, and enzymes.
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|---|---|
| ln Vitro |
While haloperidol potentiates the reduction in 5-equilibrium tryptophan induced by mesolimbic brain regions, it has no effect on 5-HT and dopamine (DA) synthesis per se. Externally, PD 144418 supplementation increased N-methyl-D-aspartate (NMDA)-induced cyclic GMP (cGMP) in cerebellar slices without affecting basal levels, suggesting that the σ1 site may regulate glutamine-induced PD 144418.
In vitro, PD-144418 binds to the sigma 1 receptor with exceptionally high affinity (Ki = 0.08 nM) and shows >3000-fold selectivity over sigma 2 (Ki = 1377 nM). The compound displays no significant activity at dopaminergic, adrenergic, muscarinic, or a variety of other receptors, ion channels, and enzymes. This selectivity profile makes it a valuable tool for studying σ1 receptor function. |
| ln Vivo |
Single anti-mescaline-induced scratching is treated with PD 144418 (10 mg/kg; i.p.; constant CD-1 mice) at a dose that does not change spontaneous locomotor activity; PD 144418 has an ED50 value of 7.0 mg/kg IP [
In vivo, PD-144418 antagonizes mescaline-induced scratching in mice following intraperitoneal administration and attenuates cocaine-induced hyperactivity in mice. The compound shows highly potential antipsychotic activity. These effects are consistent with modulation of σ1 receptor signaling in the central nervous system. |
| Enzyme Assay |
Specific cell-free receptor binding assay protocols for PD-144418 involve competitive radioligand binding assays using membranes expressing σ1 or σ2 receptors. Ki values are determined by measuring displacement of a radiolabeled σ receptor ligand (such as [³H]-(+)-pentazocine for σ1). Selectivity is confirmed by screening against a panel of other receptors, ion channels, and enzymes.
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| Cell Assay |
In vitro cell-based assays for PD-144418 use cell lines expressing σ1 receptors. Cells are treated with PD-144418, and σ1 receptor-mediated signaling is assessed by measuring calcium mobilization, or by evaluating the compound's effects on cellular stress responses and ion channel modulation.
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| Animal Protocol |
Animal/Disease Models: Male CD-1 mice induced with mescaline[1]
Doses: 10 mg/kg Route of Administration: intraperitoneal (ip) injection Experimental Results: Antagonizes mescaline-induced induction at a dose that does not alter spontaneous locomotor activity Scratching. In vivo animal studies for PD-144418 have been conducted in mouse models. The compound is administered intraperitoneally, and its effects on mescaline-induced scratching and cocaine-induced hyperactivity are assessed. These studies demonstrate the compound's antipsychotic potential and its ability to modulate σ1 receptor-mediated behaviors. |
| ADME/Pharmacokinetics |
PD-144418 oxalate has a molecular formula of C20H24N2O5 and a molecular weight of 372.42 g/mol. The chemical name is 1,2,3,6-tetrahydro-5-[3-(4-methylphenyl)-5-isoxazolyl]-1-propyl-pyridine oxalate. Purity is typically ≥98%. The compound is soluble in DMSO. Storage: at -20°C, protected from light.
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| Toxicity/Toxicokinetics |
Specific toxicological data for PD-144418 are not detailed in the available literature. The compound is classified for research use only and is not intended for human therapeutic applications. As a σ1 receptor ligand, potential toxicities may relate to effects on central nervous system function.
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| References | |
| Additional Infomation |
PD-144418 (CAS 154130-99-1) is a novel, high-affinity σ1 receptor ligand with a Ki of 0.08 nM and >3000-fold selectivity over σ2 (Ki = 1377 nM). It shows no significant affinity for other receptors, ion channels, or enzymes. In vivo, it antagonizes mescaline-induced scratching and attenuates cocaine-induced hyperactivity in mice. No clinical trial data are available.
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| Molecular Formula |
C18H22N2O.C2H2O4
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|---|---|
| Molecular Weight |
372.41496
|
| Exact Mass |
372.169
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| CAS # |
154130-99-1
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| Related CAS # |
PD 144418 oxalate;1794760-28-3
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| PubChem CID |
9817231
|
| Appearance |
White to light yellow solid-liquid Mixture
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| LogP |
3.242
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
|
| Heavy Atom Count |
21
|
| Complexity |
360
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC1C=CC(C2C=C(C3CN(CCC)CCC=3)ON=2)=CC=1
|
| InChi Key |
FOQRKFCLRMMKAT-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C18H22N2O/c1-3-10-20-11-4-5-16(13-20)18-12-17(19-21-18)15-8-6-14(2)7-9-15/h5-9,12H,3-4,10-11,13H2,1-2H3
|
| Chemical Name |
3-(4-methylphenyl)-5-(1-propyl-3,6-dihydro-2H-pyridin-5-yl)-1,2-oxazole
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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 : ~100 mg/mL (~354.13 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.85 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 (8.85 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6852 mL | 13.4261 mL | 26.8521 mL | |
| 5 mM | 0.5370 mL | 2.6852 mL | 5.3704 mL | |
| 10 mM | 0.2685 mL | 1.3426 mL | 2.6852 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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