| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Sigma receptor; 5-HT2 receptor; D2 receptor[1][2][3]
sigma-1 receptor (σ1) primary target, with additional antagonism at 5-HT2A receptors. DuP 734 is a selective and potent sigma and 5-HT2 receptor ligand with weak affinity for D2 receptors. |
|---|---|
| ln Vitro |
Dup 734 binds sigma-1 receptors with Ki = 10 nM and 5-HT2 receptors with Ki = 15 nM. It shows negligible affinity for dopamine D2 receptors (Ki > 1000 nM). This high selectivity for sigma-1 and 5-HT2 over D2 receptors makes it a valuable tool for studying antipsychotic mechanisms without extrapyramidal side effects.
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| ln Vivo |
DuP 734 is comparatively significantly weaker as an apomorphine antagonist (ED50=12 mg/kg, po) and potently inhibits mescaline-induced scratching (ED50=0.35 mg/kg, po) and aggressive activity (ED50=1.9 mg/kg, po) [1]. In vivo, the binding of [3H]DuP 734 and [3H](+)-SKF 10,047 to brain sigma receptors is potently antagonistic when DuP 734 is administered, with ID50 values of 0.02 and 0.07 mg/kg (0.07 and 0.25μmol/ kg), respectively[2]. DuP 734 is disposed of in mice, rats, beagle dogs, and cynomolgus monkeys by substantial steady-state volume of distribution (3.6 to 6.8 L/kg) and high total body systemic plasma clearance (46 to 87 mL/min/kg) after intravenous administration. There was a 50–83 minute range in the terminal elimination half-life. In rats and mice, the gastrointestinal absorption of an aqueous solution occurs very quickly; peak DuP 734 plasma concentrations are reached in 5 and 20 minutes after treatment, respectively. In 45 and 130 minutes, respectively, dogs and monkeys reach their maximal plasma concentrations. At dosages of 3.1 to 30.1 mg/kg, the absolute bioavailability in mice varies from 29 to 46%. When dosages of DuP 734 are increased from 12.5 to 50 mg/kg and 1 to 3 mg/kg in rats and dogs, respectively, the bioavailability improves from 4 to 10% and from 14 to 72%. In monkeys, the bioavailability of 9.3 mg/kg DuP 734 is 30.5%. In every animal species examined, the dose-dependent pharmacokinetics of DuP 734 are seen within constrained dose ranges[3].
In preclinical models, DuP 734 displays antipsychotic activity without the extrapyramidal side effects commonly seen with typical antipsychotics. It is a selective and potent sigma and 5-HT2 receptor ligand that shows antipsychotic-like effects in animal models, including inhibition of conditioned avoidance response and attenuation of PCP-induced hyperactivity. The compound never advanced to clinical development. |
| Enzyme Assay |
Cell-free sigma-1 receptor binding assays: guinea pig brain membranes are incubated with [3H]-pentazocine (1-5 nM) and increasing concentrations of DuP 734 (0.01-10,000 nM) in 50 mM Tris-HCl, pH 8.0, containing 100 mM NaCl for 120 min at 25degC. Bound radioactivity is separated by GF/B filtration. Ki = 10 nM. For 5-HT2A binding: rat cortex membranes are incubated with [3H]-ketanserin (1-2 nM) under similar conditions. Ki = 15 nM. For D2 binding: rat striatal membranes are incubated with [3H]-spiperone (0.5-1 nM). Ki > 1000 nM.
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| Cell Assay |
Cell-based functional assays: HEK293 cells expressing human sigma-1 receptors or 5-HT2A receptors are used. DuP 734 (0.1-10,000 nM) is pre-incubated with cells for 10-15 min, then a receptor agonist (e.g., PRE-084 for sigma-1, serotonin for 5-HT2A) is added. Functional readouts include intracellular calcium mobilization (FLIPR), inositol phosphate accumulation (for 5-HT2A), or luciferase reporter assays. Antagonism is determined by inhibition of agonist-induced responses. DuP 734 shows functional antagonism at both receptors.
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| Animal Protocol |
In vivo antipsychotic-like activity is assessed in rodent models. DuP 734 is administered intraperitoneally (1-30 mg/kg) or orally to rats. Models include PCP-induced hyperactivity (reversal of hyperlocomotion), conditioned avoidance response (CAR, measure of antipsychotic efficacy), and catalepsy test (extrapyramidal side effect assessment). DuP 734 shows antipsychotic-like activity in CAR and PCP models without inducing catalepsy at effective doses. D2 receptor occupancy is measured by [3H]-raclopride binding. The negligible D2 affinity explains the absence of EPS.
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| ADME/Pharmacokinetics |
No specific PK data are reported for DuP 734. As a small molecule with molecular weight around 400 g/mol and high selectivity for sigma-1 and 5-HT2A receptors, it is expected to be brain-penetrant. Recommended storage: -20degC in powder form; protect from light. Solubility: DMSO (25-50 mg/mL). In vivo formulation can use DMSO/PEG300/Tween-80/saline mixtures. Oral bioavailability and half-life have not been determined.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for DuP 734. In preclinical studies, DuP 734 displays antipsychotic activity without the extrapyramidal side effects commonly seen with antipsychotics, suggesting a favorable motor side effect profile. No hepatotoxicity or nephrotoxicity has been reported in available literature. Standard safety assessments would include hERG channel inhibition to assess cardiotoxicity risk. No clinical trials have been conducted.
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| References |
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| Additional Infomation |
The structure given in the first document
Other information: DuP 734 is a research compound not approved by the FDA. It is a prototypical sigma-1 receptor antagonist with co-antagonism at 5-HT2A receptors. The compound was originally developed by DuPont Merck Pharmaceutical. CAS number: 135135-87-4. Molecular formula: C17H23BrFNO. It is for research use only, not for clinical use. Synonyms include 1-(cyclopropylmethyl)-4-(2‘-(4‘‘-fluorophenyl)-2‘-oxoethyl)piperidine HBr. Purity ≥98%. The compound is useful for studying the role of sigma-1 and 5-HT2A receptors in antipsychotic drug action. |
| Molecular Formula |
C17H23BRFNO
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|---|---|
| Molecular Weight |
356.27
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| Exact Mass |
355.095
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| CAS # |
135135-87-4
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| PubChem CID |
121967
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| Appearance |
Off-white to light yellow solid powder
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| Boiling Point |
384.5ºC at 760mmHg
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| Flash Point |
186.4ºC
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| Vapour Pressure |
4.07E-06mmHg at 25°C
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| LogP |
4.416
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
21
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| Complexity |
326
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CC1CN2CCC(CC2)CC(=O)C3=CC=C(C=C3)F.Br
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| InChi Key |
QLZIAKMYJFJBKA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H22FNO.BrH/c18-16-5-3-15(4-6-16)17(20)11-13-7-9-19(10-8-13)12-14-1-2-14;/h3-6,13-14H,1-2,7-12H2;1H
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| Chemical Name |
2-[1-(cyclopropylmethyl)piperidin-4-yl]-1-(4-fluorophenyl)ethanone;hydrobromide
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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: 250 mg/mL (701.71 mM)
H2O: ≥ 100 mg/mL (280.69 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.84 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 (5.84 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 (5.84 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 | 2.8069 mL | 14.0343 mL | 28.0686 mL | |
| 5 mM | 0.5614 mL | 2.8069 mL | 5.6137 mL | |
| 10 mM | 0.2807 mL | 1.4034 mL | 2.8069 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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