Otenabant (CP-945598) HCl

Alias: CP-945,598; CP 945,598; CP-945598; Otenabant HCl; CP945598; CP 945598; CP945,598

Cat No.:V1518 Purity: ≥98%

COA Product Data Instructions for use SDS

Otenabant (CP-945598) HCl Chemical Structure CAS No.: 686347-12-6
Product category: Cannabinoid Receptor

This product is for research use only, not for human use. We do not sell to patients.

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Other Forms of Otenabant (CP-945598) HCl:

Otenabant (CP-945598)

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Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

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J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Clinical Trial Information

Product Description

Otenabant HCl (also known as CP-945,598; CP 945,598; CP-945598), the hydrochloride salt of Otenabant, is a novel, potent and highly selective cannabinoid receptor CB1 antagonist with potential anti-obesity effect. It exhibits >10,000-fold higher selectivity against CB2 receptor and inhibits CB1 with a Ki of 0.7 nM. Pfizer developed otenabant with the intention of treating obesity; however, the drug's development has been shelved because of issues with rimonabant, a comparable medication, during clinical trials.

Biological Activity I Assay Protocols (From Reference)

Targets

hCB1 ( Ki = 0.7 nM ); rCB1 ( Ki = 2.8 nM )

ln Vitro

In vitro activity: Otenabant HCl has a low affinity for human CB2 receptors, with a Ki of 7.6 μM[1]. Otenabant HCl inhibits the CB1 receptor with low hERG affinity, sufficient CNS penetration, and moderate unbound microsomal clearance[2].

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 (10-10M to 10-5 M), the assay mix is challenged with the cannabinoid agonist CP-55,940 (10 μM). For one hour, assays are conducted at 30°C. The FlashPlates are subsequently centrifuged for 10 minutes at 2000 g. Next, utilizing a Wallac Microbeta, the stimulation of GTPγ [35S] binding is measured. GraphPad Prism is used to calculate EC50. The absence of an agonist is used to measure inverse agonism.

Animal Protocol

The 14-week-old male C57/Bl6/6J mice were chosen for the DIO weight loss study after they were fed a high-fat diet (45% kcal from fat) for six weeks. The age-matched, chow-fed control animals' mean body weight is at least five standard deviations out of the range for the animal weights. Mouse housing is done in pairs. All animals weigh 38.9±0.5 g on average when they first start. Day 0: Treatment groups (n = 10 per group) are randomly assigned to mice. Over ten days, mice are given a daily dose of either vehicle or 10 mg/kg (p.o.) CP-945,598. The dosing occurs roughly half an hour before the start of the 12-hour dark cycle. Food consumption and BW are tracked every day. Daily and cumulative FI and cumulative BW measurements are computed along with an analysis of variance and a comparison of means. Statistical significance is defined as P < 0.05.

References

[1]. In vitro and in vivo pharmacology of CP-945,598, a potent and selective cannabinoid CB1 receptor antagonist for the management of obesity. Biochemical and Biophysical Research Communications, 2010; 394;366-371.

[2]. Discovery of 1-[9-(4-chlorophenyl) -8-(2-chlorophenyl)- 9H-purin-6-yl] -4-ethylaminopiperidine-4-carboxylic acid amide hydrochloride (CP-945,598), a novel, potent, and selective cannabinoid type 1 receptor antagonist. J. Med. Chem. 2009, 52, 2, 234–237.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula

C25H26CL3N7O

Molecular Weight

546.88

Exact Mass

545.13

Elemental Analysis

C, 54.91; H, 4.79; Cl, 19.45; N, 17.93; O, 2.93

CAS #

686347-12-6

Related CAS #

Otenabant; 686344-29-6

Appearance

White solid powder

SMILES

CCNC1(CCN(CC1)C2=NC=NC3=C2N=C(N3C4=CC=C(C=C4)Cl)C5=CC=CC=C5Cl)C(=O)N.Cl

InChi Key

KPYUQCJBZGQHPL-UHFFFAOYSA-N

InChi Code

InChI=1S/C25H25Cl2N7O.ClH/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);1H

Chemical Name

1-[8-(2-chlorophenyl)-9-(4-chlorophenyl)purin-6-yl]-4-(ethylamino)piperidine-4-carboxamide;hydrochloride

Synonyms

CP-945,598; CP 945,598; CP-945598; Otenabant HCl; CP945598; CP 945598; CP945,598

HS Tariff Code

2934.99.9001

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)

Solubility Data

Solubility (In Vitro)

DMSO: 1~5 mg/mL (1.8~9.1 mM)

Water: <1 mg/mL

Ethanol: <1 mg/mL

Solubility (In Vivo)

0.5% methylcellulose: 17 mg/mL

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.8286 mL	9.1428 mL	18.2855 mL
	5 mM	0.3657 mL	1.8286 mL	3.6571 mL
	10 mM	0.1829 mL	0.9143 mL	1.8286 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.

Calculator

Mass

Concentration

Volume

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Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

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See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
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The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
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The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

Total molecular weight

g/mol

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
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The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

Dosage mg/kg

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Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

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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.

Note： (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.

Clinical Trial Information

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