| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Targets |
CB1 ( Ki = 0.7 nM )
CB1 cannabinoid receptor (antagonist). Otenabant is a potent and selective CB1 antagonist with a Ki of 0.7 nM. It exhibits >10,000-fold greater selectivity against the human CB2 receptor. Otenabant HCl has low affinity with a Ki of 7.6 μM for human CB2 receptors. The CB1 receptor is a G protein-coupled receptor that mediates the effects of endocannabinoids and is involved in appetite regulation, energy balance, and mood. By antagonizing CB1 receptors, Otenabant may reduce appetite and promote weight loss. The compound inhibits CB1 receptor with moderate unbound microsomal clearance, low hERG affinity, and adequate CNS penetration. Otenabant was developed by Pfizer for obesity treatment. |
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| ln Vitro |
Otenabant HCl has a low affinity for human CB2 receptors, with a Ki of 7.6 μM[1]. With moderate unbound microsomal clearance, low hERG affinity, and sufficient CNS penetration, otenabant HCl inhibits the CB1 receptor[2].
Otenabant is a potent CB1 receptor antagonist with a Ki of 0.7 nM. It exhibits >10,000-fold greater selectivity against the human CB2 receptor. Otenabant HCl has low affinity with a Ki of 7.6 μM for human CB2 receptors. The compound inhibits CB1 receptor with moderate unbound microsomal clearance, low hERG affinity, and adequate CNS penetration. Its high potency and selectivity make it a valuable tool for studying CB1 receptor function and the role of the endocannabinoid system in appetite regulation and energy balance. Otenabant was developed by Pfizer as a potential treatment for obesity. |
| ln Vivo |
Otenabant causes a metabolic shift toward greater fat oxidation by sharply increasing energy expenditure and lowering the respiratory quotient in rats. In a 10-day weight loss study, diet-induced obese mice treated with otenabant (10 mg/kg, p.o.) showed a 9% vehicle adjusted weight loss[1]. After administering the synthetic CB1 receptor agonist CP-55940, tenabant HCl reverses four behaviors mediated by cannabinoids: locomotor activity, hypothermia, analgesia, and catalepsy. Otenabant HCl increases energy expenditure and fat oxidation in a rodent model of acute food intake and demonstrates dose-dependent anorectic activity[2]. |
| Enzyme Assay |
Membranes are made from CHOK1 cells that have had the human CB-1 receptor cDNA transfected into them permanently. The GTPγ [35S] binding assays are carried out in duplicate in a 96-well FlashPlate format using 100 pM GTPγ [35S] and 10μg membrane per well in an assay buffer consisting of 50 mM Tris HCl, pH 7.4, 3 mM MgCl2, pH 7.4, 10 mM MgCl2, 20 mM EGTA, 100 mM NaCl, 30 µM GDP, 0.1% bovine serum albumin, and the protease inhibitors 100 μg/mL bacitracin, 100 μg/mL benzamidine, 5 μg/mL aprotinin, and 5 μg/mL leupeptin. After 10 minutes of incubation with escalating antagonist concentrations (10-10 M to 10-5 M), the assay mix is challenged with the cannabinoid agonist CP-55,940 (10 μM). Assays are run for one hour at 30°C. After that, the FlashPlates are centrifuged for 10 minutes at 2000 g. Following that, a Wallac Microbeta is used to quantify the stimulation of GTPγ [35S] binding. The EC50 is calculated with GraphPad Prism. Inverse agonism is measured in the absence of agonist.
CB1 receptor binding assays are performed using membranes prepared from cells expressing recombinant CB1 receptors or from brain tissue. Radioligand binding studies use [³H]-CP-55940 or [³H]-SR141716A as labeled ligands. Membrane preparations are incubated with varying concentrations of Otenabant and a fixed concentration of radioligand in binding buffer (50 mM Tris-HCl pH 7.4, 5 mM MgCl₂, 1 mM EDTA, 0.1% BSA) for 60-120 minutes at room temperature. Non-specific binding is determined using excess unlabeled CP-55940 or SR141716A. Bound radioactivity is measured by scintillation counting after filtration through GF/B filters. IC50 and Ki values are calculated by non-linear regression. The Ki for CB1 is 0.7 nM. |
| Cell Assay |
For the DIO weight loss study, male 14-week-old C57/Bl6/6J mice that have been fed a high-fat diet (45% kcal from fat) for six weeks are chosen. The animals' body weights differ by at least five standard deviations from the mean body weight of age-matched, chow-fed control animals. Mice live alone in enclosures. All animals have an initial weight of 38.9±0.5 g on average. Mice are randomly allocated to treatment groups on day 0 (n = 10 per group). Over the course of ten days, mice are given daily doses of vehicle or 10 mg/kg (p.o.) CP-945,598. This begins roughly thirty minutes prior to the start of the 12-hour dark cycle. Food consumption and BW are tracked every day. For daily and cumulative FI and cumulative BW measurements, analysis of variance and comparison of means are computed. It is deemed statistically significant when P < 0.05.
Cellular CB1 receptor antagonism is evaluated in cell lines expressing recombinant CB1 receptors (e.g., HEK-293 cells). Cells are cultured in appropriate media at 37°C with 5% CO₂ and treated with Otenabant at various concentrations. Functional assays measure receptor-mediated inhibition of cAMP accumulation (Gi-coupled receptor) in response to CB1 agonists (e.g., CP-55940, WIN 55,212-2). The compound's antagonist activity is assessed by its ability to reverse agonist-induced inhibition of cAMP. Cell viability is assessed using MTT or LDH assays. Each experiment includes known CB1 antagonists (e.g., rimonabant) as positive controls and vehicle controls. |
| Animal Protocol |
Dissolved in 0.5% methyl cellulose; 30 mg/kg; p.o. administration | Sprague-Dawley rats
| ADME/Pharmacokinetics |
Molecular Weight: Not fully specified. Formula: Not fully specified. CAS No.: 686344-29-6. Synonyms: CP-945598, CP945598. Appearance: Solid. Purity: Typically >98%. Solubility: Soluble in DMSO. Storage: Powder at -20°C for up to 3 years; 4°C for up to 2 years; In solvent at -80°C for up to 6 months; -20°C for up to 1 month. Otenabant is a potent and selective CB1 antagonist with a Ki of 0.7 nM.
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| Toxicity/Toxicokinetics |
No comprehensive toxicology data are publicly available for Otenabant. The compound is intended for research use only and has not undergone full preclinical toxicology evaluation required for clinical development. As a CB1 antagonist, potential adverse effects may include psychiatric effects (anxiety, depression), gastrointestinal disturbances, and other effects seen with rimonabant. Development of Otenabant was discontinued due to issues similar to those seen with rimonabant. The compound is for research use only and not for human therapeutic use.
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| References |
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| Additional Infomation |
Otenabant has been investigated for the treatment of obesity.
Mechanism of Action Preclinical and clinical trial data suggest that CB-1 antagonists may have a beneficial effect on glucose metabolism in patients with type 2 diabetes and may also be an effective treatment for obesity. Otenabant is also known as CP-945598 and CP945598. Its IUPAC name is not fully resolved in publicly available sources. Otenabant is a potent and selective CB1 antagonist with a Ki of 0.7 nM. It exhibits >10,000-fold greater selectivity against the human CB2 receptor. It was developed by Pfizer for the treatment of obesity, but development was discontinued. No regulatory approvals have been reported. Otenabant is for research use only. |
| Molecular Formula |
C25H25CL2N7O
|
|---|---|
| Molecular Weight |
510.4183
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| Exact Mass |
509.15
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| Elemental Analysis |
C, 58.83; H, 4.94; Cl, 13.89; N, 19.21; O, 3.13
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| CAS # |
686344-29-6
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| Related CAS # |
Otenabant Hydrochloride; 686347-12-6
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| PubChem CID |
10052040
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| Appearance |
White to off-white solid powder
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| Density |
1.46
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| Boiling Point |
757.891ºC at 760 mmHg
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| LogP |
5.379
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
35
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| Complexity |
729
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1=C([H])C([H])=C([H])C([H])=C1C1=NC2=C(N=C([H])N=C2N2C([H])([H])C([H])([H])C(C(N([H])[H])=O)(C([H])([H])C2([H])[H])N([H])C([H])([H])C([H])([H])[H])N1C1C([H])=C([H])C(=C([H])C=1[H])Cl
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| InChi Key |
UNAZAADNBYXMIV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H25Cl2N7O/c1-2-31-25(24(28)35)11-13-33(14-12-25)22-20-23(30-15-29-22)34(17-9-7-16(26)8-10-17)21(32-20)18-5-3-4-6-19(18)27/h3-10,15,31H,2,11-14H2,1H3,(H2,28,35)
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| Chemical Name |
1-[8-(2-chlorophenyl)-9-(4-chlorophenyl)purin-6-yl]-4-(ethylamino)piperidine-4-carboxamide
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| Synonyms |
CP945598; CP-945598; CP 945598; CP945,598; CP-945,598; CP 945,598; Otenabant
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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: ~100 mg/mL (~195.9 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3 mg/mL (5.88 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 30.0 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: ≥ 3 mg/mL (5.88 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 30.0 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: ≥ 3 mg/mL (5.88 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 | 1.9592 mL | 9.7959 mL | 19.5917 mL | |
| 5 mM | 0.3918 mL | 1.9592 mL | 3.9183 mL | |
| 10 mM | 0.1959 mL | 0.9796 mL | 1.9592 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00645463 | Completed | Drug: CP-945,598 | Obesity | Pfizer | March 2007 | Phase 1 |
| NCT00644839 | Completed | Drug: CP-945,598 | Obesity | Pfizer | April 2008 | Phase 1 |
| NCT00645216 | Completed | Drug: CP-945,598 | Obesity | Pfizer | June 2007 | Phase 1 |
| NCT00134199 | Completed | Drug: CP-945,598 Drug: sibutramine |
Obesity | Pfizer | March 2005 | Phase 2 Phase 3 |
| NCT00706537 | Completed | Drug: Active treatment Drug: Placebo |
Non-Alcoholic Steatohepatitis (NASH) |
Pfizer | July 2008 | Phase 1 |
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