Taranabant  (Synonyms: MK-0364)

Taranabant is a highly potent and selective cannabinoid 1 (CB1) receptor inverse agonist that inhibits the binding and functional activity of various agonists, with a binding K_i of 0.13 nM for the human CB1R in vitro.

IC50: 0.3 nM (hCB1R), 0.4 nM (rCB1R)^[1]
Ki: 0.13 nM (hCB1R), 0.27 nM (rCB1R)^[1]

Taranabant (MK-0364) binds to human or rat CB1R with an IC₅₀ of 0.3 and 0.4 nM, respectively, corresponding to a K_i value of 0.13 and 0.27 nM, respectively. Taranabant binds to the human or rat CB2R with an IC₅₀ value of 290 and 470 nM, respectively, corresponding to a K_i value of 170 and 310 nM, respectively. The selectivity ratio of CB1R over CB2R is approximately 1000-fold^[1]. Taranabant (MK-0364) is a novel, acyclic cannabinoid-1 receptor inverse agonist for the treatment of obesity. IC₅₀s of Taranabant for CB1R and CB2R by substituted amides is 0.3±0.1 nM, and 290±60 nM, respectively. Taranabant is a CB1R inverse agonist with minimal potential for covalent protein binding. Taranabant is an exceptionally potent and selective (900-fold over CB2) CB1R inverse agonist with >500-fold improvement in affinity over the original lead. In a functional assay of cyclic-AMP production, Taranabant is determined to be an inverse agonist (EC₅₀=2.4±1.4 nM)^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Taranabant (MK-0364) dose-dependently inhibits 2 h and overnight food intake as well as overnight gains in body weight in C57BL/6N mice. At the 1- and 3-mg/kg doses (p.o.), Taranabant significantly inhibits 2-h food intake (36 and 69% reductions, respectively; P<0.05 and P<0.00001, respectively) and overnight food intake (13 and 40% reductions, respectively; P<0.05 and P<0.00001, respectively) as well as overnight gains in body weight (48 and 165% reductions, respectively; P<0.01 and P<0.00001, respectively). Taranabant dose-dependently inhibits food intake and weight gain, with an acute minimum effective dose of 1 mg/kg in diet-induced obese (DIO) rats^[1]. Taranabant (MK-0364) has a good pharmacokinetic profile in three species (rat, 1 mg/kg iv, 2 mg/kg po, F=74%, t_1/2=2.7 h; dog, 0.2 mg/kg iv, 0.4 mg/kg po, F=31%; t_1/2=14 h; rhesus monkey, 0.2 mg/kg iv, 0.4 mg/kg po, F=31%, t_1/2=3.6 h) and good brain exposure (1 mg/kg iv, brain and plasma concentrations of 0.11 and 0.18 μM at 1 h, respectively)^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

515.95

C₂₇H₂₅ClF₃N₃O₂

701977-09-5

Solid

White to off-white

ClC1=CC=C(C[C@@H](C2=CC=CC(C#N)=C2)[C@@H](NC(C(C)(OC3=CC=C(C=N3)C(F)(F)F)C)=O)C)C=C1

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

• [1]. Fong TM, et al. Antiobesity Efficacy of a Novel Cannabinoid-1 Receptor Inverse Agonist, N-[(1S,2S)-3-(4-Chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2 -methyl-2-{[5-(trifluoromethyl)pyridin-2-yl]oxy}propanamide (MK-0364), in Rodents. J Pharmacol Exp T  [Content Brief]

  [2]. Lin LS, et al. Discovery of N-[(1S,2S)-3-(4-Chlorophenyl)-2- (3-cyanophenyl)-1-methylpropyl]-2-methyl-2- {[5-(trifluoromethyl)pyridin-2-yl]oxy}propanamide (MK-0364), a novel, acyclic cannabinoid-1 receptor inverse agonist for the treatment of obesity. J M  [Content Brief]