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| 1mg |
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| Other Sizes |
| Targets |
Pimozide-d4-1 targets the dopamine D2 receptor (D2R) as a potent antagonist. The parent compound, Pimozide, exhibits Ki values of 1.4 nM, 2.5 nM, and 588 nM for dopamine D2, D3, and D1 receptors, respectively. It also has high affinity for the alpha1-adrenoceptor with a Ki of 39 nM. Additionally, Pimozide is an inhibitor of the transcription factors STAT3 and STAT5. Pimozide-d4-1, due to its identical chemical structure except for the isotope substitution, binds to these same targets with similar affinities, though the presence of deuterium may slightly alter the kinetics in vivo. The primary use of the deuterated version is as an internal standard for bioanalysis.
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as tracers for quantification throughout the drug development process. Due to its potential to alter the pharmacokinetic and metabolic characteristics of medications, deuteration has drawn attention[4].
Pimozide-d4-1 is not typically used in vitro to assess biological activity, as the unlabeled Pimozide is used for that purpose. However, the labeled version would be expected to exhibit the same in vitro activities as the parent compound. Pimozide acts as a potent dopamine D2 receptor antagonist (Kis: 1.4 nM for D2, 2.5 nM for D3, 588 nM for D1). It also inhibits alpha1-adrenoceptor (Ki 39 nM) and the transcription factors STAT3 and STAT5 at higher concentrations, contributing to its anti-proliferative effects. In cell-based assays, Pimozide inhibits dopamine-mediated signaling, leading to a reduction in prolactin secretion, and it can suppress the growth of certain cancer cells, such as glioma or neuroblastoma cells, by inhibiting STAT3/5 signaling. |
| ln Vivo |
Pimozide-d4-1 is not used in animal efficacy studies; rather, it is an analytical standard. The parent compound, Pimozide, is an orally active typical antipsychotic used clinically for Tourette syndrome and chronic schizophrenia. In vivo, Pimozide has a long duration of action due to its long half-life (≈ 28-55 hours in humans). It penetrates the blood-brain barrier and blocks central dopamine D2 receptors. Its antiemetic and antipsychotic effects are a result of D2 antagonism in the chemoreceptor trigger zone and mesolimbic/mesocortical pathways. The antitumor activity of Pimozide has been demonstrated in preclinical mouse xenograft models of glioma, neuroblastoma, and breast cancer, where it inhibits tumor growth via STAT3/5 inhibition.
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| Enzyme Assay |
Pimozide-d4-1 is not used for in vitro enzyme binding or receptor binding assays in a typical drug discovery context; its primary use is as an analytical internal standard. To set up an LC-MS/MS method for quantifying Pimozide in plasma, a stock solution of Pimozide-d4-1 is prepared in methanol or acetonitrile (e.g., 1 mg/mL). The internal standard is then diluted to a working concentration (e.g., 10-100 ng/mL) in the same solvent. A fixed volume (e.g., 10 uL) of the internal standard solution is added to each biological sample (e.g., 50 uL of plasma) after the addition of the calibration standards. Samples are extracted by protein precipitation (e.g., adding 3-5 volumes of acetonitrile containing 0.1% formic acid), vortexed, and centrifuged. The supernatant is transferred to an autosampler vial and injected into the LC-MS/MS system. Separation is achieved on a C18 column with a gradient of water (0.1% formic acid) and acetonitrile (0.1% formic acid). Detection is performed in positive electrospray ionization (ESI+) mode with multiple reaction monitoring (MRM) for m/z 461 → 98 for Pimozide and m/z 465 → 102 for the d4-internal standard (or another appropriate transition). The peak area ratio of Pimozide to internal standard is plotted against the known concentration of Pimozide in the calibration standards to generate a standard curve.
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| Cell Assay |
Pimozide-d4-1 is not used for cell-based studies. A typical protocol for assessing Pimozide's cellular activity, however, is as follows: cancer cells (e.g., U87-MG glioma or SH-SY5Y neuroblastoma cells) are seeded in 96-well plates at a density of 5,000-10,000 cells/well in appropriate medium. After 24 h, the cells are treated with Pimozide (as a reference standard, not the d4 version) at concentrations ranging from 0.1-30 uM. The compound is dissolved in DMSO, and the final DMSO concentration in the culture medium should be less than 0.1%. After 48-72 h, cell viability is assessed using the MTT assay. For mechanistic studies, cells are treated with Pimozide (5-20 uM) for 4-24 h. Protein lysates are prepared and analyzed by Western blotting for the expression of total and phosphorylated STAT3 (p-STAT3, Y705), STAT5, and downstream targets such as Bcl-xL, Mcl-1, and cyclin D1. This protocol is for the unlabeled Pimozide.
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| Animal Protocol |
Pimozide-d4-1 is exclusively used as an internal standard for in vivo pharmacokinetic studies. A standard PK protocol for the unlabeled parent drug (Pimozide) can be described as follows: Male Sprague-Dawley rats (200-250 g, n=5 per group) are administered a single oral (p.o.) dose of Pimozide (1-5 mg/kg in 0.5% methylcellulose) or an intravenous (i.v.) dose (0.5-1 mg/kg in a suitable vehicle with a cosolvent). Blood samples (approximately 200-300 uL) are collected via the jugular vein or tail vein at pre-dose and at multiple time points post-dose (e.g., 0.5, 1, 2, 4, 6, 8, 12, 24, 48, and 72 h). Plasma is separated by centrifugation. A fixed concentration of Pimozide-d4-1 (e.g., 20 ng/mL) is added to each sample as an internal standard. The samples are processed by liquid-liquid extraction (e.g., with methyl tert-butyl ether) or solid-phase extraction (SPE) and analyzed by LC-MS/MS. PK parameters are calculated using non-compartmental analysis (NCA).
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| ADME/Pharmacokinetics |
No specific toxicity data are reported for the deuterated internal standard. The parent compound, Pimozide, is an FDA-approved antipsychotic with a well-established safety profile. Its adverse effects are related to its pharmacological activities and include extrapyramidal symptoms (e.g., tardive dyskinesia, dystonia, parkinsonism), sedation, weight gain, and cardiovascular effects, such as QT prolongation (which can be serious). Pimozide carries a black box warning for QT prolongation, torsades de pointes, and sudden death. The deuterated version is used as an analytical standard and is not administered in vivo for pharmacological purposes. The small amounts used as an internal standard in bioanalytical workflows do not pose any additional safety risks beyond those associated with standard chemical handling.
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| Toxicity/Toxicokinetics |
Pimozide-d4-1 is a research-grade stable isotope-labeled compound used as an internal standard in LC-MS/MS methods for the quantification of Pimozide in biological samples. The parent compound, Pimozide, is a potent dopamine receptor antagonist with Kis of 1.4 nM, 2.5 nM, and 588 nM for dopamine D2, D3, and D1 receptors, respectively, and also inhibits STAT3/STAT5 signaling. This product is for research use only and is not intended for human therapeutic applications.
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| References |
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| Molecular Formula |
C28H25D4F2N3O
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| Related CAS # |
Pimozide;2062-78-4;Pimozide-d4;1803193-57-8
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| Appearance |
Typically exists as solid at room temperature
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
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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