Rimonabant

Summary

Rimonabant (CHEMBL111) is an approved small-molecule anti-obesity agent (ATC A08AX01) targeting GPR55 and CNR1; indicated across 17 conditions including obesity disorder and cardiovascular disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: A08AX01
• Targets: 2 (GPR55, CNR1)
• Indications: 17 conditions
• Clinical trials: 46
• Chemistry: 463.8 Da · C22H21Cl3N4O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL111
Name	Rimonabant
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	104850
ChEBI	CHEBI:34967
ATC	A08AX01
Molecular formula	C22H21Cl3N4O
Molecular weight	463.8
InChIKey	JZCPYUJPEARBJL-UHFFFAOYSA-N

SMILES: CC1=C(N(N=C1C(=O)NN2CCCCC2)C3=C(C=C(C=C3)Cl)Cl)C4=CC=C(C=C4)Cl

IUPAC name: 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-piperidin-1-ylpyrazole-3-carboxamide

ChEBI definition: A carbohydrazide obtained by formal condensation of the carboxy group of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid with the amino group of 1-aminopiperidine. It is a potent and selective cannabinoid receptor 1 (CB1R) antagonist. Besides its antagonistic properties, numerous studies have shown that, at micromolar concentrations rimonabant behaves as an inverse agonist at CB1 receptors. The drug was the first selective CB1 antagonist/inverse agonist introduced into clinical practice to treat obesity and metabolic-related disorders. It was later withdrawn from market due to CNS-related adverse effects including depression and suicidal ideation.

Pharmacological roles (ChEBI): anti-obesity agent, CB1 receptor antagonist, appetite depressant.

Also known as: Acomplia, Rimonabant, SR-14171, SR-141716, SR-141716A, SR141716, Zimulti, rimonabant, SID26757994, RIMONABANT, SID144205753, Riminabant

Parent form; salt/anhydrous children: CHEMBL558598

Patent coverage: 3,909 distinct patent families (15,726 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 15,526 (99%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
GPR55	GPR55	Antagonist	6.55	0%	Q9Y2T6
CNR1	CB1 receptor	Antagonist	8.7	0%	P21554

Broader ChEMBL bioactivity targets: 43 (assay-derived). Sample: G-protein coupled receptor 55, ATP-binding cassette sub-family C member 4, 5-hydroxytryptamine receptor 2B, Vasopressin V1a receptor, Cholecystokinin receptor type A, Alpha-2C adrenergic receptor, Histamine H2 receptor, Alpha-2B adrenergic receptor, Equilibrative nucleoside transporter 1, Bile acid receptor.

Bioactivity

ChEMBL activities: 260 potent at pChembl ≥ 5 of 287 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CNR1	9.96	EC50	0.11	nM	CHEMBL_ACT_3198590
P20272	9.77	EC50	0.17	nM	CHEMBL_ACT_2188942
CNR1	9.72	Ki	0.19	nM	CHEMBL_ACT_2249687
P20272	9.51	Ki	0.31	nM	CHEMBL_ACT_2358196
CNR1	9.4	Ki	0.4	nM	CHEMBL_ACT_2360124
CNR1	9.37	Ki	0.43	nM	CHEMBL_ACT_2358150
P20272	9.19	Ki	0.65	nM	CHEMBL_ACT_2249671
CNR1	9.15	Ki	0.7	nM	CHEMBL_ACT_18673994
CNR1	9.14	Ki	0.73	nM	CHEMBL_ACT_7850122
CNR1	9.13	Ki	0.74	nM	CHEMBL_ACT_3198563
CNR1	9.05	Ki	0.9	nM	CHEMBL_ACT_2249679
P20272	9.05	Ki	0.9	nM	CHEMBL_ACT_3014397
CNR1	9.03	Ki	0.93	nM	CHEMBL_ACT_6161497
CNR1	9	Ki	1	nM	CHEMBL_ACT_1680873
CNR2	8.96	Ki	1.1	nM	CHEMBL_ACT_14729940
CNR1	8.96	Ki	1.1	nM	CHEMBL_ACT_1898177
CNR1	8.93	Ki	1.18	nM	CHEMBL_ACT_2349292
CNR1	8.93	Ki	1.18	nM	CHEMBL_ACT_3517602
P20272	8.93	Ki	1.18	nM	CHEMBL_ACT_657380
P20272	8.89	Ki	1.3	nM	CHEMBL_ACT_1012596
CNR1	8.87	IC50	1.35	nM	CHEMBL_ACT_2358193
CNR1	8.86	Ki	1.38	nM	CHEMBL_ACT_3228942
CNR1	8.85	Ki	1.4	nM	CHEMBL_ACT_6165332
P47746	8.82	Ki	1.5	nM	CHEMBL_ACT_12707567
CNR1	8.82	EC50	1.5	nM	CHEMBL_ACT_13893534
CNR1	8.82	IC50	1.5	nM	CHEMBL_ACT_25598454
CNR1	8.8	Ki	1.6	nM	CHEMBL_ACT_10979846
CNR1	8.8	Ki	1.6	nM	CHEMBL_ACT_2525616
CNR1	8.8	Ki	1.6	nM	CHEMBL_ACT_3014396
CNR1	8.74	Ki	1.8	nM	CHEMBL_ACT_10979891

Target pathways

Aggregated over 2 target gene(s): GPR55, CNR1.

Top Reactome pathways

2 total, by targets touching each:

Pathway	Targets	Genes
Class A/1 (Rhodopsin-like receptors)	2	CNR1, GPR55
G alpha (i) signalling events	2	CNR1, GPR55

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor signaling pathway	2
signal transduction	2
cannabinoid signaling pathway	2
phospholipase C-activating G protein-coupled receptor signaling pathway	1
positive regulation of Rho protein signal transduction	1
bone resorption	1
negative regulation of osteoclast differentiation	1
positive regulation of ERK1 and ERK2 cascade	1
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
axonal fasciculation	1
glucose homeostasis	1
retrograde trans-synaptic signaling by endocannabinoid	1
regulation of presynaptic cytosolic calcium ion concentration	1

Indications & clinical

Indications

17 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
obesity disorder	4	MONDO:0011122	EFO:0001073
cardiovascular disorder	3	MONDO:0004995	EFO:0000319
metabolic syndrome X	3	MONDO:0011565	EFO:0000195
fatty liver disease	3	MONDO:0004790	HP:0001397
prediabetes syndrome	3	MONDO:0006920	EFO:1001121
coronary artery disorder	3	MONDO:0005010	MONDO:0021661
arteriosclerosis disorder	3	MONDO:0002277	EFO:0009086
type 2 diabetes mellitus	3	MONDO:0005148	MONDO:0005148
Prader-Willi syndrome	3	MONDO:0008300	MONDO:0008300
nicotine dependence	2	MONDO:0008575	EFO:0003768
spinal cord injury	2	MONDO:0043797	EFO:1001919
cannabis dependence	1	MONDO:0005689	EFO:0007191

5 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 46.

Phase distribution

Phase	Trials
PHASE3	35
PHASE2	5
PHASE4	2
PHASE1	2
PHASE1/PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00584389	PHASE4	TERMINATED	The Effect of Rimonabant on Energy Expenditure, Fat Metabolism and Body Composition
NCT00734123	PHASE4	UNKNOWN	Early Detection of Atherosclerosis: a Randomized Trial in the Primary Prevention of Cardiovascular Diseases.
NCT00029835	PHASE3	COMPLETED	Obese Patients With Untreated Dyslipidemias
NCT00029848	PHASE3	COMPLETED	Obese Patients With Type 2 Diabetes
NCT00029861	PHASE3	COMPLETED	Obese Patients With or Without Comorbidities (RIO-North America)
NCT00124332	PHASE3	COMPLETED	STRADIVARIUS (Strategy To Reduce Atherosclerosis Development InVolving Administration of Rimonabant - the Intravascular Ultrasound Study)
NCT00228176	PHASE3	TERMINATED	Atherosclerosis Underlying Development Assessed by Intima-Media Thickness in Patients on Rimonabant
NCT00239967	PHASE3	COMPLETED	An International Study of Rimonabant in Dyslipidemia With AtheroGenic Risk In Abdominally Obese Patients
NCT00257257	PHASE3	COMPLETED	Study Evaluating Rimonabant Efficacy in Drug-NAive DiabEtic Patients
NCT00263042	PHASE3	TERMINATED	Comprehensive Rimonabant Evaluation Study of Cardiovascular ENDpoints and Outcomes
NCT00288236	PHASE3	COMPLETED	Study Evaluating Rimonabant Efficacy in Insulin-Treated Diabetic Patients(ARPEGGIO)
NCT00299325	PHASE3	COMPLETED	VIsceral Fat Reduction Assessed by CT-scan On RImonabAnt
NCT00325546	PHASE3	COMPLETED	Study of Weight-Reducing Effect and Safety of Rimonabant In Obesity in ASIA (RIO-ASIA)
NCT00325650	PHASE3	TERMINATED	Rimonabant In Prediabetic Subjects To Delay Onset Of Type 2 Diabetes
NCT00358228	PHASE3	COMPLETED	Comparison of the Efficacy and Safety of 2 Oral Doses of Rimonabant, 5 mg/Day or 20 mg/Day, Versus Placebo, as an Aid to Smoking Cessation (STRATUS US)
NCT00386061	PHASE3	COMPLETED	Rimonabant in Obesity Over a 2-Year Duration (RIO-Europe)
NCT00405808	PHASE3	TERMINATED	Rimonabant in Abdominally Obese Patients With Impaired Fasting Blood Glucose
NCT00408148	PHASE3	TERMINATED	High Density Lipoprotein Turnover
NCT00412698	PHASE3	TERMINATED	European Trial About Effect of RimoNabant on Abdominal Obese Patients With dysLipidemia
NCT00434096	PHASE3	TERMINATED	Japanese Study of Rimonabant in Obese Patients With Dyslipidemia (VENUS)
NCT00449605	PHASE3	TERMINATED	A Glycemic Control Evaluation of Glimepiride Versus Rimonabant on Top of Metformin in Type 2 Diabetes
NCT00458081	PHASE3	TERMINATED	Evaluation of the Rimonabant Impact on the Regression of Asymptomatic Damage Caused by Cardiovascular Risk Factors
NCT00458718	PHASE3	COMPLETED	Efficacy and Safety of Rimonabant as an Aid to Smoking Cessation With or Without Nicotine Patch
NCT00459173	PHASE3	COMPLETED	Efficacy and Safety of Rimonabant as an Aid to Maintenance of Smoking Cessation
NCT00464165	PHASE3	COMPLETED	Comparison of Efficacy and Safety of Rimonabant 5mg/Day or 20mg/Day Versus Placebo in Smoking Cessation
NCT00464256	PHASE3	COMPLETED	Comparison of Efficacy and Safety of Rimonabant 20mg/Day Versus Placebo in Smoking Cessation
NCT00478595	PHASE3	TERMINATED	Japanese Study With Rimonabant in Obese Type 2 Diabetic Patients With Oral Anti-diabetic Drug
NCT00478972	PHASE3	TERMINATED	Japanese Study With Rimonabant in Obese Type 2 Diabetic Patients on Diet and Exercise
NCT00481923	PHASE3	COMPLETED	Efficacy and Safety of Rimonabant With or Without Hypocaloric Diet in Obese Patients
NCT00481975	PHASE3	COMPLETED	Efficacy and Safety of Rimonabant on Weight Loss and Frequency of Binge Episodes in Obese Patients
NCT00546325	PHASE3	COMPLETED	REASSURE: The Effect of Rimonabant on HbA1c in Overweight or Obese Patients With Type 2 Diabetes Not Adequately Controlled on 2 Oral Antidiabetic Agents
NCT00576667	PHASE3	TERMINATED	An Efficacy and Safety Study of Rimonabant for Treatment of Nonalcoholic Steatohepatitis (NASH) in Patients Without Diabetes
NCT00577148	PHASE3	TERMINATED	An Efficacy and Safety Study of Rimonabant for Treatment of Nonalcoholic Steatohepatitis (NASH) in Patients With Type 2 Diabetes
NCT00603109	PHASE3	TERMINATED	Effect of Rimonabant on Weight Gain and Body Composition in Adults With Prader Willi Syndrome
NCT00678483	PHASE3	TERMINATED	Long-Term Effect of 10 mg Versus 20 mg Rimonabant in Overweight or Obese Patients
NCT00690456	PHASE3	TERMINATED	Effect of Rimonabant and Metformin Combination on Glycemic Control in Patients With Type 2 Diabetes
NCT00754689	PHASE3	WITHDRAWN	Study of Rimonabant/Metformin Combinations to Investigate Diabetes (Blood Sugar) Control in Patients With Type 2 Diabetes
NCT00075205	PHASE2	COMPLETED	Rimonabant to Reduce Alcohol Consumption
NCT00459004	PHASE2	COMPLETED	Japanese Dose-Response Study of Rimonabant in Obese Patients
NCT00547118	PHASE2	TERMINATED	The Effects of Rimonabant, on Weight and Metabolic Risk Factors

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

127 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
CANNABIDIOL	ChEMBL + PubChem	Phase 4 (approved)	CNR1, GPR55
DRONABINOL	ChEMBL + PubChem	Phase 4 (approved)	CNR1, GPR55
CANNABIDIVARIN	ChEMBL	Phase 2	CNR1, GPR55
TETRAHYDROCANNABIVARIN	ChEMBL	Phase 2	CNR1, GPR55
TAFAMIDIS	ChEMBL + PubChem	Phase 4 (approved)	CNR1
ACARBOSE	ChEMBL	Phase 4 (approved)	CNR1
ALCLOMETASONE DIPROPIONATE	ChEMBL	Phase 4 (approved)	CNR1
ALPRAZOLAM	ChEMBL	Phase 4 (approved)	CNR1
AMCINONIDE	ChEMBL	Phase 4 (approved)	CNR1
AMPRENAVIR	ChEMBL	Phase 4 (approved)	CNR1
ATENOLOL	ChEMBL	Phase 4 (approved)	CNR1
BECLOMETHASONE DIPROPIONATE	ChEMBL	Phase 4 (approved)	CNR1
BEPRIDIL	ChEMBL	Phase 4 (approved)	CNR1
BIFONAZOLE	ChEMBL	Phase 4 (approved)	CNR1
BISACODYL	ChEMBL	Phase 4 (approved)	GPR55
BUCLIZINE	ChEMBL	Phase 4 (approved)	CNR1
BUSPIRONE	ChEMBL	Phase 4 (approved)	CNR1
CAFFEINE	ChEMBL	Phase 4 (approved)	CNR1
CALCITRIOL	ChEMBL	Phase 4 (approved)	CNR1
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	CNR1
CARBENOXOLONE	ChEMBL	Phase 4 (approved)	CNR1
CEFDINIR	ChEMBL	Phase 4 (approved)	CNR1
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	CNR1
CICLESONIDE	ChEMBL	Phase 4 (approved)	CNR1
DEXAMETHASONE	ChEMBL	Phase 4 (approved)	CNR1
ECONAZOLE	ChEMBL	Phase 4 (approved)	CNR1
EFAVIRENZ	ChEMBL	Phase 4 (approved)	CNR1
ENZALUTAMIDE	ChEMBL	Phase 4 (approved)	CNR1
ERYTHROMYCIN	ChEMBL	Phase 4 (approved)	CNR1
ETHAMBUTOL	ChEMBL	Phase 4 (approved)	CNR1
FELODIPINE	ChEMBL	Phase 4 (approved)	CNR1
FENOFIBRATE	ChEMBL	Phase 4 (approved)	CNR1
FENTICONAZOLE	ChEMBL	Phase 4 (approved)	CNR1
FEXOFENADINE	ChEMBL	Phase 4 (approved)	CNR1
FLUOXETINE	ChEMBL	Phase 4 (approved)	CNR1
FLUSPIRILENE	ChEMBL	Phase 4 (approved)	CNR1
FLUTICASONE FUROATE	ChEMBL	Phase 4 (approved)	CNR1
GLIPIZIDE	ChEMBL	Phase 4 (approved)	CNR1
IMIPRAMINE	ChEMBL	Phase 4 (approved)	CNR1
INDOCYANINE GREEN ACID FORM	ChEMBL	Phase 4 (approved)	CNR1
KETOTIFEN	ChEMBL	Phase 4 (approved)	CNR1
LOFEPRAMINE	ChEMBL	Phase 4 (approved)	CNR1
LORCASERIN	ChEMBL	Phase 4 (approved)	CNR1
LOSARTAN	ChEMBL	Phase 4 (approved)	CNR1
MASOPROCOL	ChEMBL	Phase 4 (approved)	CNR1
MECLIZINE	ChEMBL	Phase 4 (approved)	CNR1
MEFLOQUINE	ChEMBL	Phase 4 (approved)	CNR1
MESTRANOL	ChEMBL	Phase 4 (approved)	CNR1
MIANSERIN	ChEMBL	Phase 4 (approved)	CNR1
MICONAZOLE	ChEMBL	Phase 4 (approved)	CNR1
MINAPRINE	ChEMBL	Phase 4 (approved)	CNR1
MITOTANE	ChEMBL	Phase 4 (approved)	CNR1
NABILONE	ChEMBL	Phase 4 (approved)	CNR1
NAFTIFINE	ChEMBL	Phase 4 (approved)	CNR1
NEBIVOLOL	ChEMBL	Phase 4 (approved)	CNR1
NIMODIPINE	ChEMBL	Phase 4 (approved)	CNR1
NISOLDIPINE	ChEMBL	Phase 4 (approved)	CNR1
ORLISTAT	ChEMBL	Phase 4 (approved)	CNR1
PAROXETINE	ChEMBL	Phase 4 (approved)	CNR1
PERHEXILINE	ChEMBL	Phase 4 (approved)	GPR55