Taranabant

Research use only, not for human use.

A potent, selective and orally active cannabinoid-1 receptor (CB1R) inverse agonist with IC50 of 2.8 nM, Ki of 0.13 nM.

A potent, selective and orally active cannabinoid-1 receptor (CB1R) inverse agonist with IC50 of 2.8 nM, Ki of 0.13 nM; displays >1000-fold selectivity over CB2R (Ki=170 nM), AT1R, NK2R, A3R, MT1R, D1R, etc.; dose-dependently inhibits food intake and weight gain in diet-induced obese (DIO) rats with an acute minimum effective dose of 1 mg/kg and has good pharmacokinetic.Obesity Phase 3 Discontinued.

Taranabant (MK-0364) binds to human or rat CB1R with an IC50 of 0.3 and 0.4 nM, respectively, corresponding to a Ki 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 Ki value of 170 and 310 nM, respectively. The selectivity ratio of CB1R over CB2R is approximately 1000-fold. 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).

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. Taranabant (MK-0364) has a good pharmacokinetic profile in three species (rat, 1 mg/kg iv, 2 mg/kg po, F=74%, t1/2=2.7 h; dog, 0.2 mg/kg iv, 0.4 mg/kg po, F=31%; t1/2=14 h; rhesus monkey, 0.2 mg/kg iv, 0.4 mg/kg po, F=31%, t1/2=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).

MK-0364 | MK0364

GPCR/G Protein

Cannabinoid Receptor

Cannabinoid Receptor

Metabolic Disease

Obesity

701977-09-5

515.9545

C27H25ClF3N3O2

>98% (HPLC)

DMSO: ≥ 42 mg/mL

CC(OC1=NC=C(C(F)(F)F)C=C1)(C)C(N[C@H]([C@H](C2=CC=CC(C#N)=C2)CC3=CC=C(Cl)C=C3)C)=O

Propanamide, N-[(1S,2S)-3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-methyl-2-[[5-(trifluoromethyl)-2-pyridinyl]oxy]-

(-20℃)

With Ice Pack

≥ 2 years