| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
Translocator protein (TSPO), also known as the 18 kDa translocator protein or peripheral benzodiazepine receptor (PBR). TSPO is a mitochondrial outer membrane protein involved in cholesterol transport, steroidogenesis, and neuroinflammation. Activation of TSPO leads to increased neurosteroid synthesis and modulation of GABAergic transmission. ONO-2952 is a TSPO antagonist (inhibitor) that blocks TSPO-mediated neurosteroid accumulation and noradrenaline release in the brain, reducing stress responses.
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| ln Vitro |
ONO-2952 binds to rat and human TSPO with Ki values ranging from 0.33 to 9.30 nM, demonstrating high potency and selectivity. The compound is more selective for TSPO than other receptors, transporters, ion channels, and enzymes. In cultured microglia, ONO-2952 inhibits the production of cytokines (TNF-alpha, IL-6, IL-1beta) and reactive oxygen species (ROS) induced by lipopolysaccharide (LPS), demonstrating anti-neuroinflammatory activity.
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| ln Vivo |
In rodent stress models, ONO-2952 (orally administered) inhibits both neurosteroid accumulation and noradrenaline release in the brain of rats exposed to acute stress. The inhibitory effect of ONO-2952 on stress-induced noradrenaline release is attenuated by co-treatment with the TSPO agonist CB34 in a dose-dependent manner, confirming target-specific activity. ONO-2952 also ameliorates stress-induced stool abnormality and abdominal pain in rodent stress models, supporting its potential for treating IBS and related stress disorders.
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| Enzyme Assay |
For TSPO binding assays, membrane fractions from rat or human tissues (e.g., brain, adrenal gland) or recombinant TSPO are incubated with the radioligand [3H]-PK11195 (1-2 nM) and varying concentrations of test compound in assay buffer. After incubation at 25degC for 60-90 minutes, bound and free radioligand are separated by rapid filtration through GF/B filters. Radioactivity is counted to calculate Ki values using Cheng-Prusoff equation. ONO-2952 shows Ki values of 0.33-9.30 nM.
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| Cell Assay |
For neuroinflammatory assays, murine BV-2 microglial cells or primary microglia are seeded in 96-well plates and pre-incubated with ONO-2952 (0.1 nM to 1 uM) for 1 hour. Cells are then stimulated with LPS (100 ng/mL) for 6-24 hours. Supernatants are collected, and TNF-alpha, IL-6, and IL-1beta levels are measured by ELISA. Reactive oxygen species (ROS) production is measured using DCFH-DA (2′,7′-dichlorofluorescin diacetate) fluorescent dye. Nitric oxide (NO) production is measured by Griess reagent.
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| Animal Protocol |
For stress-related behavioral studies, rat models of acute stress (restraint stress, forced swim test, elevated plus maze) or chronic social defeat stress (CSDS) in mice are used. ONO-2952 is administered orally (doses 1-30 mg/kg) 30-60 minutes before stress exposure. Behavioral assessments include open field test (anxiety), forced swim test and tail suspension test (depression), and marble burying test (compulsive behavior). Brain tissue is collected for measurement of neurosteroids (allopregnanolone) and noradrenaline by LC-MS/MS or HPLC-ECD.
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| ADME/Pharmacokinetics |
TSPO antagonists including ONO-2952 are orally bioavailable and penetrate the blood-brain barrier (BBB). Brain TSPO occupancy of 50% or more is required for pharmacological effect. In positron emission tomography (PET) studies using [11C]PK11195, ONO-2952 demonstrated dose-dependent occupancy of TSPO in the brains of conscious monkeys. The compound has good metabolic stability and a half-life suitable for once-daily oral dosing. Detailed PK parameters such as Cmax, Tmax, AUC, and t1/2 are not publicly available but are consistent with once-daily oral administration based on literature reports.
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| Toxicity/Toxicokinetics |
In preclinical toxicity studies, ONO-2952 is well-tolerated at effective doses. Because TSPO is involved in steroidogenesis, long-term TSPO antagonism may theoretically affect steroid hormone synthesis, but no significant endocrine adverse effects have been reported in animal studies at therapeutic doses. No significant hepatotoxicity, nephrotoxicity, or cardiotoxicity has been observed. Comprehensive human safety data would be generated during clinical trials, but no Phase 3 results are publicly available for ONO-2952.
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| References |
[1]. Mitsui K, et al. Anti-stress effects of ONO-2952, a novel translocator protein 18 kDa antagonist, in rats. Neuropharmacology. 2015 Dec;99:51-66.
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| Additional Infomation |
ONO-2952 was developed by Ono Pharmaceutical Co., Ltd. for the treatment of stress-related disorders including generalized anxiety disorder and irritable bowel syndrome (IBS). The compound has been evaluated in Phase 2 clinical trials. A randomized, double-blind, placebo-controlled clinical trial in patients with IBS with diarrhea (IBS-D) was conducted to evaluate the efficacy, safety, and pharmacokinetics of ONO-2952. Results showed that ONO-2952 was well-tolerated and improved abdominal pain/discomfort and bowel habits in IBS-D patients. This product is for research use only.
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| Molecular Formula |
C22H20CLFN2O2
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|---|---|
| Molecular Weight |
398.86
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| Related CAS # |
ONO-2952;895169-20-7
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| Appearance |
White to off-white solid powder
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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 :~220 mg/mL (~551.57 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5.5 mg/mL (13.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 55.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5071 mL | 12.5357 mL | 25.0715 mL | |
| 5 mM | 0.5014 mL | 2.5071 mL | 5.0143 mL | |
| 10 mM | 0.2507 mL | 1.2536 mL | 2.5071 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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