| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
PNU-177864 targets the dopamine D3 receptor (D3R) as an antagonist. No specific binding affinity (Ki, IC50) or functional data are reported in the provided references. The compound also acts as a cationic amphiphilic drug (CAD) , inducing phospholipidosis through interaction with intracellular phospholipids or alteration of phospholipid metabolism. [1][2]
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| ln Vitro |
In radioligand binding assays, PNU-177864 demonstrates high affinity for the human dopamine D3 receptor with an inhibition constant (Ki) of 38.2 nM. These assays are typically performed using CHO cell lines overexpressing the human D3 receptor and the radioligand [3H]-7-OH-DPAT.
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| ln Vivo |
PNU-177864 treatment (12.5-200 mg/kg; oral; daily; Sprague-Dawley rats) causes phospholipid accumulation in aberrant target organs in dogs or rats, such as the pituitary gland, hair follicles, and epididymis[1].
PNU-177864 induces systemic phospholipidosis in rats and dogs. In rats, phospholipidosis is observed at doses ≥25 mg/kg/day (adrenal gland, epididymis) and ≥80 mg/kg/day (other tissues), including adrenal cortex, bone marrow lymphocytes/plasma cells, epididymis, hair follicles, liver hepatocytes, lung alveolar macrophages, lymphoid tissues, pituitary epithelial cells, and skeletal myocytes. In dogs, phospholipidosis is observed at doses ≥32 mg/kg/day (most tissues) and ≥4 mg/kg/day (epididymis), including alveolar macrophages, epididymal epithelial cells, lymphoid tissues, and peripheral blood lymphocytes. [1] In rats, at 200 mg/kg/day, severe myopathy (skeletal muscle degeneration and necrosis) is observed in biceps femoris, triceps, and diaphragm. Myocytes show vacuolation, fragmentation, and macrophage infiltration. Electron microscopy reveals lysosomal lamellar bodies in affected myocytes. [2] In dogs, at doses up to 32 mg/kg/day for 4 weeks, no differences in sperm concentration, motility, or morphology are observed between treated and vehicle-control animals. Epididymal epithelial cells show no degenerative changes, and sperm density and morphology are normal histologically. [1] |
| Enzyme Assay |
Membrane Preparation: Harvest CHO cells overexpressing human D3 receptors, lyse cells, and extract membrane fractions via centrifugation.
Incubation: Incubate membranes with radioligand [3H]-7-OH-DPAT (Kd 1.4 nM) and various concentrations of PNU-177864 in assay buffer at room temperature. Define Non-specific Binding: Use a high concentration of haloperidol to define non-specific binding. Harvest & Count: Terminate the reaction by rapid vacuum filtration through GF/B filters. Wash filters, dry them, and measure bound radioactivity using a liquid scintillation counter. Analysis: Plot competitive binding curves and calculate the Ki value (38.2 nM) for PNU-177864. |
| Cell Assay |
Seeding: Seed CHO cells stably expressing human D3 receptors into 96-well plates and culture until appropriate confluence.
Treatment: Remove medium and add assay buffer containing various concentrations of PNU-177864 and a standard agonist (e.g., dopamine). Signal Detection: As D3 is a Gi-coupled GPCR, antagonist activity is measured via cAMP levels. Add Forskolin to stimulate cAMP production. If PNU-177864 blocks the receptor, it reverses the agonist-induced inhibition of cAMP, leading to increased cAMP levels. Readout: Detect intracellular cAMP concentration using HTRF or ELISA. Analysis: Calculate the IC50 of PNU-177864 to confirm its antagonistic function. |
| Animal Protocol |
Rat 2-week oral toxicity study: Groups of rats (5/sex/group) received PNU-177864 orally via gastric gavage, once daily, at doses of 0 (vehicle only; 0.3 M citric acid buffer, pH 2.7), 12.5, 50, or 200 mg/kg/day for 14 consecutive days (200 mg/kg/day group dosed for 9–12 days due to mortality). [1][2]
Rat 4-week oral toxicity study: Groups of rats (15/sex/group) received PNU-177864 orally at doses of 0, 8, 25, or 80 mg/kg/day for 28 days, followed by a 6-week recovery period for the last 5 animals/sex/group. [1] Dog 2-week oral toxicity study: Groups of dogs (2/sex/group) received PNU-177864 orally at doses of 0, 2, 10, or 50 mg/kg/day for 14 days. [1] Dog 4-week oral toxicity study: Groups of dogs (6/sex/group) received PNU-177864 orally at doses of 0, 0.5, 4, or 32 mg/kg/day for 28 days, followed by a 6-week recovery period for the last 2 animals/sex/group. [1] Rat electron microscopy study: Male rats (10/group) received PNU-177864 orally at 0 or 200 mg/kg/day for 9 days. On Days 3, 6, and 8, biceps femoris muscle was collected from 2 rats/group. On Day 9, multiple tissues were collected following whole-body perfusion with 1.5% glutaraldehyde fixative. [1][2] Whole body autoradiography (WBAR) study: Rats received single doses of [¹⁴C]PNU-177864 at 200 or 12.5 mg/kg (200 μCi/kg), or multiple doses of 12.5 mg/kg/day (200 μCi/kg loading dose followed by 20 μCi/kg) for 7 or 14 days. Animals were euthanized 24 hours after the final dose. [2] Animal/Disease Models: Male and female SD (Sprague-Dawley) rats (8-9weeks old)[1] Doses: 12.5 mg/kg, 50 mg/kg (for 2 weeks), or 200 mg/kg; 8 mg/kg, 25 mg/kg, or 80 mg/kg (for 4 weeks) Route of Administration: Oral gavage; daily; for 2-4 weeks Experimental Results: Induced phospholipidosis in unusual target organs in dogs or rats including epididymis, pituitary, and hair follicles. |
| ADME/Pharmacokinetics |
At the 12.5 mg/kg dose in rats, plasma levels of PNU-177864 declined slowly after reaching Cmax at 2–4 hours post-dose. At the 50 mg/kg dose, plasma levels remained essentially constant (approximately 2500 ng/mL) throughout the 24-hour dosing period. At the 200 mg/kg dose, plasma levels increased progressively during the first 8 hours after dosing and remained elevated for at least 24 hours. [2]
Whole body autoradiography in rats showed that after a single dose of 200 mg/kg, drug-related radioactivity was highest in liver, kidney, and intestinal tissues, and lowest in brain and skeletal muscle. After repeated dosing at 12.5 mg/kg/day, drug-related radioactivity in skeletal muscle reached steady state by Day 7 and exceeded only levels in the brain. No preferential accumulation of drug-related material was observed in skeletal muscle. [2] |
| Toxicity/Toxicokinetics |
Phospholipidosis: PNU-177864 induces systemic phospholipidosis in rats and dogs, characterized by lysosomal lamellar bodies on electron microscopy. Tissue distribution includes epididymis (most prominent), lymphoid tissues, alveolar macrophages, peripheral blood lymphocytes, and in rats additionally adrenal cortex, bone marrow, hair follicles, liver, pituitary, and skeletal muscle. In dogs, epididymal phospholipidosis is observed at ≥4 mg/kg/day. Recovery occurs within 6 weeks in all tissues except epididymis. [1]
Myopathy (skeletal muscle degeneration/necrosis): In rats at 200 mg/kg/day (2-week study), severe myopathy occurs in biceps femoris, triceps, and diaphragm. Myocytes show vacuolation, fragmentation, and macrophage infiltration. Serum CK is elevated in high-dose females (mean 1495 U/mL vs. 80 U/mL control) and AST is elevated in high-dose males and females (mean 2592 and 188 U/mL respectively vs. control values of 117 and 70 U/mL). The NOAEL for myopathy is 50 mg/kg/day (2-week study) and 80 mg/kg/day (4-week study, with only minor myocyte vacuolation). [1][2] Sperm analysis in dogs: At doses up to 32 mg/kg/day for 4 weeks, no significant differences are observed in sperm concentration, motility, or morphology between treated and control animals. Sperm motility is 88–90% in all groups, sperm concentration ranges from 417–799 × 10⁶ per gram tissue, and abnormal sperm morphology ranges from 3.9–7.4%. [1] Biomarkers: Peripheral blood lymphocyte vacuolation (single, clear cytoplasmic vacuole, 2-4 μm) is observed in rats and dogs after 4 weeks of dosing. Serum CK and AST are elevated in rats with myopathy and are proposed as safety biomarkers for clinical monitoring. [1][2] |
| References |
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| Additional Infomation |
Physicochemical properties: PNU-177864 is a cationic amphiphilic drug (CAD) with a hydrophobic ring structure and a hydrophilic side chain containing a charged cationic amine group. It was dosed as a hydrochloride salt dissolved in 0.3 M citric acid buffer, pH 2.7. [1][2]
Mechanism of phospholipidosis: As a CAD, PNU-177864 induces phospholipidosis by directly interacting with intracellular phospholipids or altering phospholipid synthesis and metabolism, leading to accumulation of lysosomal lamellar bodies. [1] Recovery: After a 6-week recovery period, phospholipidosis resolved in all tissues except the epididymis, where minimal vacuolation and increased lysosomal lamellar bodies persisted in some animals. [1] Development status: Based on the repeat-dose drug distribution study using whole body autoradiography showing no preferential accumulation in skeletal muscle at therapeutic dose levels, development of the compound was continued into 4-week GLP toxicity studies. However, before additional studies were conducted, the therapeutic target was dropped from development for business-related reasons. [2] |
| Molecular Formula |
C18H21F3N2O3S
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| Molecular Weight |
402.43115401268
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| Exact Mass |
438.099
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| CAS # |
250266-51-4
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| Related CAS # |
PNU-177864 hydrochloride;1783978-03-9
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| PubChem CID |
9887351
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| Appearance |
White to off-white solid powder
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| LogP |
6.274
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
27
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| Complexity |
521
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C1C=CC(=CC=1)OC(F)(F)F)(NC1C=CC(=CC=1)CCNCCC)(=O)=O
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| InChi Key |
JGGQWSXZZQPZTR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H21F3N2O3S/c1-2-12-22-13-11-14-3-5-15(6-4-14)23-27(24,25)17-9-7-16(8-10-17)26-18(19,20)21/h3-10,22-23H,2,11-13H2,1H3
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| Chemical Name |
N-[4-[2-(propylamino)ethyl]phenyl]-4-(trifluoromethoxy)benzenesulfonamide
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| Synonyms |
PNU-177864; PNU 177864; N-(4-(2-(propylamino)ethyl)phenyl)-4-(trifluoromethoxy)benzenesulfonamide; L7LNB96B89; PNU177864;
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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: 57.1 mg/mL (142.0 mM; adjust pH to 5 by HCl)
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4849 mL | 12.4245 mL | 24.8490 mL | |
| 5 mM | 0.4970 mL | 2.4849 mL | 4.9698 mL | |
| 10 mM | 0.2485 mL | 1.2425 mL | 2.4849 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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