| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
ONO-2952 targets the translocator protein 18 kDa (TSPO), also known as the peripheral benzodiazepine receptor (PBR). TSPO is involved in steroidogenesis and neuroinflammation, and its antagonism modulates the stress response. ONO-2952 is a potent and selective TSPO antagonist with Ki values of 0.330-9.30 nM for rat and human TSPO.
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| ln Vitro |
Regarding TSPO selectivity, ONO-2952 demonstrated high TSPO selectivity versus 98 off-targets (<50% inhibition) at a dose of 10 μM. Only three receptors (melatonin 2, progesterone B, and epinephrine α2C) exhibited Ki values less than 1 μM, according to the determination of ONO-2952 Ki or IC50 values (50% inhibition at 10 μM) for the remaining 35 targets. Compared to TSPO, ONO-2952's affinity for these receptors is at least 59 times lower. Compared to TSPO, the ONO-2952 GABAA receptor has a Ki value that is more than 600 times greater [1].
In vitro, ONO-2952 acts as a potent and selective TSPO antagonist with Ki values of 0.330-9.30 nM for rat and human TSPO. Its in vitro activity is assessed using radioligand binding assays to measure its affinity for TSPO. The compound's selectivity for TSPO over other receptors is also evaluated. |
| ln Vivo |
In rats with more than 50% brain TSPO occupancy, treatment with ONO-2952 (0.03-3 mg/kg; oral; male Sprague Dawley rats) dose-dependently reduces the defecation produced by restraint stress. Additionally, ONO-2952 can prevent rats from freezing when they experience conditioned fear stress [1]. In the brains of acutely stressed rats, ONO-2952 blocks the release of norepinephrine and the buildup of neurosteroids [1].
In vivo activity of ONO-2952 has been demonstrated in rat models, where it suppresses conditioned fear stress-induced freezing behavior with efficacy equivalent to that of diazepam, but without affecting learning and memory. It exerts its anti-stress effects through inhibition of excessive activation of the noradrenergic system in the brain without amnesic effects. |
| Enzyme Assay |
The in vitro receptor binding assay for ONO-2952 involves measuring its affinity for TSPO using radioligand binding techniques. These assays use membrane preparations from tissues expressing TSPO, such as the brain or peripheral tissues, and measure the displacement of a labeled ligand by the compound. Ki values of 0.330-9.30 nM for rat and human TSPO are determined. Selectivity over other receptors is also assessed.
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| Cell Assay |
In vitro cellular assays for ONO-2952 are performed using cells expressing TSPO, such as glial cells or macrophages. These assays measure the compound's ability to antagonize TSPO-mediated effects, such as steroidogenesis or neuroinflammation. The compound's potent and selective TSPO antagonism is demonstrated by its ability to inhibit TSPO ligand binding and downstream signaling.
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| Animal Protocol |
Animal/Disease Models: Male Sprague Dawley rats (8 weeks old) conditioned fear stress test [1]
Doses: 0.03 mg/kg, 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg Route of Administration: Orally Experimental Results:Dose-dependent inhibition of restraint stress-induced defecation in rats. And inhibits freezing behavior in rats induced by conditioned fear stress. In vivo animal studies for ONO-2952 are conducted in rat models of conditioned fear stress. These studies typically involve oral administration of the compound, followed by assessment of freezing behavior, a measure of fear response. The compound suppresses freezing behavior with efficacy equivalent to diazepam, but without affecting learning and memory. These studies demonstrate its anti-stress effects and favorable profile. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of ONO-2952 are characterized by oral activity and bioavailability. As an orally active compound, it is designed for systemic administration and has favorable ADME properties. Its pharmacokinetic profile supports its development for the treatment of IBS and stress-related disorders. The compound's ability to cross the blood-brain barrier enables its central nervous system effects.
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| Toxicity/Toxicokinetics |
Toxicology studies of ONO-2952 have been conducted to evaluate its safety profile. As a TSPO antagonist, its toxicology profile includes effects on steroidogenesis and neuroinflammation. Preclinical toxicology studies include acute and repeat-dose toxicity assessments, as well as evaluations of central nervous system and endocrine function. The compound is generally well-tolerated at therapeutic doses.
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| References | |
| Additional Infomation |
ONO-2952 is being studied in the clinical trial NCT01887002 (a study evaluating the effect of ONO-2952 on pain perception caused by rectal distension in female patients with diarrhea-predominant irritable bowel syndrome (IBS-D)).
ONO-2952 is a potent, selective, and orally active TSPO antagonist being developed for the treatment of irritable bowel syndrome (IBS) and stress-related disorders. It exerts its anti-stress effects through inhibition of excessive activation of the noradrenergic system in the brain without amnesic effects. Its efficacy in suppressing conditioned fear stress-induced freezing behavior is equivalent to diazepam. |
| Molecular Formula |
C22H20CLFN2O2
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|---|---|
| Molecular Weight |
398.86
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| Exact Mass |
398.119
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| CAS # |
895169-20-7
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| Related CAS # |
(R)-ONO-2952
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| PubChem CID |
11524127
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
609.4±55.0 °C at 760 mmHg
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| Flash Point |
322.3±31.5 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.682
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| LogP |
4.15
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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 |
2
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| Heavy Atom Count |
28
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| Complexity |
630
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC(=O)N1CC2(CC2)C3=C([C@@H]1C4=C(C=C(C=C4)Cl)OC)NC5=C3C(=CC=C5)F
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| InChi Key |
ZBQMTQGDBFZUBG-NRFANRHFSA-N
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| InChi Code |
InChI=1S/C22H20ClFN2O2/c1-12(27)26-11-22(8-9-22)19-18-15(24)4-3-5-16(18)25-20(19)21(26)14-7-6-13(23)10-17(14)28-2/h3-7,10,21,25H,8-9,11H2,1-2H3/t21-/m0/s1
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| Chemical Name |
1-[(1S)-1-(4-chloro-2-methoxyphenyl)-5-fluorospiro[3,9-dihydro-1H-pyrido[3,4-b]indole-4,1'-cyclopropane]-2-yl]ethanone
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| Synonyms |
ONO 2952; ONO2952; ONO-2952
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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 : ~180 mg/mL (~451.29 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 4.5 mg/mL (11.28 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 45.0 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: ≥ 4.5 mg/mL (11.28 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 45.0 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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