Orlistat

Summary

Orlistat (CHEMBL175247) is an approved small-molecule EC 3.1.1.3 (triacylglycerol lipase) inhibitor (ATC A08AB01) targeting DAGLA, DAGLB, and PNLIP; indicated across 5 conditions including obesity disorder and infertility disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: A08AB01
• Targets: 5 (DAGLA, DAGLB, PNLIP…)
• Indications: 5 conditions
• Clinical trials: 53
• Chemistry: 495.7 Da · C29H53NO5

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL175247
Name	Orlistat
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	3034010
ChEBI	CHEBI:94686
ATC	A08AB01
Molecular formula	C29H53NO5
Molecular weight	495.7
InChIKey	AHLBNYSZXLDEJQ-FWEHEUNISA-N

SMILES: CCCCCCCCCCC[C@@H](C[C@H]1[C@@H](C(=O)O1)CCCCCC)OC(=O)[C@H](CC(C)C)NC=O

IUPAC name: [(2S)-1-[(2S,3S)-3-hexyl-4-oxooxetan-2-yl]tridecan-2-yl] (2S)-2-formamido-4-methylpentanoate

ChEBI definition: A carboxylic ester resulting from the formal condensation of the carboxy group of N-formyl-L-leucine with the hydroxy group of (3S,4S)-3-hexyl-4-[(2S)-2-hydroxytridecyl]oxetan-2-one. A pancreatic lipase inhibitor, it is used as an anti-obesity drug.

Pharmacological roles (ChEBI): EC 3.1.1.3 (triacylglycerol lipase) inhibitor, EC 2.3.1.85 (fatty acid synthase) inhibitor, anti-obesity agent.

Other ChEBI roles (chemical / environmental): bacterial metabolite.

Also known as: Alli, Alli (previously orlistat gsk), Beacita, Lipstatin, NSC-758881, Orlipastat, Orlistat, RO-180647002, Tetrahydrolipstatin, Xenical, orlistat, tetrahydrolipstatin

Patent coverage: 11,062 distinct patent families (38,186 SureChEMBL compound mentions), from 1 matched compound structure(s). 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
DAGLA	diacylglycerol lipase α	Inhibition	7.2	0.2%	Q9Y4D2
DAGLB	diacylglycerol lipase β	Inhibition	7	1.3%	Q8NCG7
PNLIP	pancreatic lipase	Inhibition	8.9	0%	P16233
FASN	fatty acid synthase	Inhibition	5.87	21.1%	P49327
ABHD12	αβ-Hydrolase 12	Inhibition	7.1	0.2%	Q8N2K0

Broader ChEMBL bioactivity targets: 20 (assay-derived). Sample: Microtubule-associated protein tau, Ferritin light chain, Pancreatic triacylglycerol lipase, Pancreatic triacylglycerol lipase, Lipoprotein lipase, Menin/Histone-lysine N-methyltransferase MLL, Hepatic triacylglycerol lipase, Cannabinoid receptor 1, Monoacylglycerol lipase ABHD6, Acetylcholinesterase, Fatty-acid amide hydrolase 1, Nuclear receptor subfamily 1 group I member 2, Platelet-activating factor acetylhydrolase, Fatty acid synthase, Endothelial lipase, Diacylglycerol lipase-alpha, Lysophosphatidylserine lipase ABHD12, Diacylglycerol lipase-beta, Diacylglycerol lipase-alpha, Phosphatidylserine lipase ABHD16A.

Bioactivity

ChEMBL activities: 54 potent at pChembl ≥ 5 of 57 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
PNLIP	8.8	IC50	1.57	nM	CHEMBL_ACT_25484988
LIPC	8.52	IC50	3	nM	CHEMBL_ACT_19172662
P00591	8.4	IC50	4	nM	CHEMBL_ACT_18706121
P00591	8.4	IC50	4	nM	CHEMBL_ACT_18706974
PNLIP	8.22	IC50	6	nM	CHEMBL_ACT_19172658
LIPG	8.22	IC50	6	nM	CHEMBL_ACT_19172678
DAGLA	8	IC50	10	nM	CHEMBL_ACT_12106509
P97612	8	IC50	10	nM	CHEMBL_ACT_12106622
P00591	7.92	IC50	12	nM	CHEMBL_ACT_16583595
ABHD6	7.88	IC50	13.18	nM	CHEMBL_ACT_15710123
ABHD6	7.85	IC50	14.13	nM	CHEMBL_ACT_15710126
ABHD6	7.7	IC50	19.95	nM	CHEMBL_ACT_15710129
Q6WQJ1	7.7	IC50	20	nM	CHEMBL_ACT_16482086
ABHD16A	7.52	IC50	30	nM	CHEMBL_ACT_2583434
PNLIP	7.48	IC50	33	nM	CHEMBL_ACT_25598739
ABHD6	7.43	IC50	37.15	nM	CHEMBL_ACT_15710132
ABHD6	7.32	IC50	47.86	nM	CHEMBL_ACT_15176646
ABHD6	7.32	IC50	48	nM	CHEMBL_ACT_15176679
ABHD6	7.32	IC50	48	nM	CHEMBL_ACT_25004900
PLA2G7	7.3	IC50	50	nM	CHEMBL_ACT_2583437
DAGLA	7.22	IC50	60	nM	CHEMBL_ACT_2583076
DAGLB	7.22	IC50	60	nM	CHEMBL_ACT_2583077
LPL	7.18	IC50	66	nM	CHEMBL_ACT_19172660
ABHD12	7.1	IC50	80	nM	CHEMBL_ACT_2583435
P00591	6.82	IC50	150	nM	CHEMBL_ACT_25545991
ABHD16A	6.77	IC50	170	nM	CHEMBL_ACT_18946650
ABHD12	6.72	IC50	190.6	nM	CHEMBL_ACT_15176647
ABHD12	6.72	IC50	190	nM	CHEMBL_ACT_15176680
ABHD12	6.72	IC50	190.6	nM	CHEMBL_ACT_15710163
ABHD12	6.72	IC50	190	nM	CHEMBL_ACT_15710164
PNLIP	6.72	IC50	190	nM	CHEMBL_ACT_18407182
P00591	6.66	IC50	220	nM	CHEMBL_ACT_12064704
FASN	6.55	Ki	280	nM	CHEMBL_ACT_12079782
P00591	6.52	IC50	300	nM	CHEMBL_ACT_10859743
P00591	6.52	IC50	300	nM	CHEMBL_ACT_15240735
P00591	6.5	IC50	320	nM	CHEMBL_ACT_15696991
P00591	6.44	IC50	360	nM	CHEMBL_ACT_18706158
P00591	6.4	IC50	400	nM	CHEMBL_ACT_19196082
DAGLB	6.38	IC50	420	nM	CHEMBL_ACT_16482130
P00591	6.22	IC50	600	nM	CHEMBL_ACT_12686384
P00591	6.22	IC50	600	nM	CHEMBL_ACT_17763594
P00591	6.22	IC50	600	nM	CHEMBL_ACT_5240357
PNLIP	6.11	IC50	780	nM	CHEMBL_ACT_23183054
P00591	6.1	IC50	800	nM	CHEMBL_ACT_18407173
P00591	6	IC50	990	nM	CHEMBL_ACT_16825183
P00591	6	IC50	990	nM	CHEMBL_ACT_18265652
DAGLA	6	IC50	1000	nM	CHEMBL_ACT_2469581
NR1I2	5.8	EC50	1600	nM	CHEMBL_ACT_15465498
MEN1	5.7	Potency	1995	nM	CHEMBL_ACT_4562684
MEN1	5.7	Potency	1995	nM	CHEMBL_ACT_4570178
CNR1	5.6	Ki	2500	nM	CHEMBL_ACT_2469583
FASN	5.33	IC50	4630	nM	CHEMBL_ACT_18094317
ACHE	5.2	AC50	6279	nM	CHEMBL_ACT_25142742
P00591	5.01	Ki	9800	nM	CHEMBL_ACT_16825163

Target pathways

Aggregated over 5 target gene(s): DAGLA, DAGLB, PNLIP, FASN, ABHD12.

Top Reactome pathways

27 total, by targets touching each:

Pathway	Targets	Genes
Arachidonate production from DAG	3	ABHD12, DAGLA, DAGLB
Hemostasis	1	ABHD12
Effects of PIP2 hydrolysis	1	ABHD12
Developmental Biology	1	PNLIP
Metabolism	1	PNLIP
Signal Transduction	1	ABHD12
ChREBP activates metabolic gene expression	1	FASN
Digestion of dietary lipid	1	PNLIP
Metabolism of vitamins and cofactors	1	PNLIP
Vitamin B5 (pantothenate) metabolism	1	FASN
Visual phototransduction	1	PNLIP
Activation of gene expression by SREBF (SREBP)	1	FASN
Signaling by GPCR	1	ABHD12
GPCR downstream signalling	1	ABHD12
G alpha (q) signalling events	1	ABHD12
Metabolism of fat-soluble vitamins	1	PNLIP
Fatty acyl-CoA biosynthesis	1	FASN
Platelet activation, signaling and aggregation	1	ABHD12
Digestion	1	PNLIP
Digestion and absorption	1	PNLIP
NR1H2 & NR1H3 regulate gene expression linked to lipogenesis	1	FASN
Sensory Perception	1	PNLIP
Developmental Cell Lineages	1	PNLIP
Retinoid metabolism and transport	1	PNLIP
Dengue Virus-Host Interactions	1	FASN
Dengue Virus Genome Translation and Replication	1	FASN
Developmental Lineage of Pancreatic Acinar Cells	1	PNLIP

Dominant GO biological processes

GO term	Targets
lipid metabolic process	5
arachidonate metabolic process	3
lipid catabolic process	3
monoacylglycerol biosynthetic process	2
neuroblast proliferation	2
diacylglycerol catabolic process	2
cannabinoid biosynthetic process	2
neurogenesis	2
regulation of inflammatory response	2
fatty acid biosynthetic process	2
retrograde trans-synaptic signaling by endocannabinoid	1
regulation of neuroinflammatory response	1
acylglycerol metabolic process	1
prostaglandin biosynthetic process	1
positive regulation of triglyceride catabolic process	1

Indications & clinical

Indications

1 approved indication. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

Indication	Phase	MONDO	EFO
obesity disorder	4	MONDO:0011122	EFO:0001073

4 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
infertility disorder	3	MONDO:0005047	EFO:0000545
polycystic ovary syndrome	2	MONDO:0008487	EFO:0000660
familial lipoprotein lipase deficiency	2	MONDO:0009387	Orphanet:411
metabolic syndrome X	1	MONDO:0011565	EFO:0000195

Clinical trials

Total trials: 53.

Phase distribution

Phase	Trials
PHASE4	19
Not specified	17
PHASE2	12
PHASE3	3
PHASE1/PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06854614	PHASE4	ACTIVE_NOT_RECRUITING	Sequential or CombinaTion Anti-obesitY Medication With Muscle Preservation for Weight Loss and MaintEnance: A PragmAtic Randomized CoNtrolled Trial (STAY-LEAN Trial)
NCT00115063	PHASE4	TERMINATED	LOSS- Louisiana Obese Subjects Study
NCT00152360	PHASE4	COMPLETED	The Effect of Xenical on Weight and Risk Factors
NCT00160407	PHASE4	COMPLETED	Orlistat (Xenical) in the Treatment of Overweight Patients With Nonalcoholic Steatohepatitis (NASH)
NCT00207311	PHASE4	COMPLETED	Study for the Treatment of Significant Steatosis With Xenical Followed by Treatment of Hepatitis C With Pegasys/Copegus
NCT00212199	PHASE4	COMPLETED	Effectiveness of Brief Counseling for Weight Management
NCT00516919	PHASE4	COMPLETED	Study of Behavioral Weight Loss Therapy for Obesity and Binge Eating in Monolingual Hispanic Persons
NCT00752726	PHASE4	COMPLETED	Effect of Orlistat in Body Composition
NCT01035333	PHASE4	COMPLETED	A Pilot Study of the Efficacy of Alli in the Management of Pre-operative Weight Loss Required for Bariatric Surgery.
NCT01475019	PHASE4	UNKNOWN	The Effect of Weight Loss on Anti-Müllerian Hormone Levels in Women With Polycystic Ovary Syndrome (PCOS)
NCT01597531	PHASE4	TERMINATED	Combinatorial Therapy for Peristent Type 2 Diabetes After Gastric Banding
NCT02041234	PHASE4	COMPLETED	Roux-en-Y Gastric Bypass for BMI 27-32 Type 2 Diabetes Versus Best Medical Treatment
NCT02706067	PHASE4	COMPLETED	Multifactorial Approach Associated With Orlistat (Xenical) for 4 Years Weight Loss Maintenance in Obese Adults
NCT03383068	PHASE4	UNKNOWN	Research of Intensive Metabolic Intervention Before Pregnancy in PCOS
NCT03582722	PHASE4	COMPLETED	Weight Loss Aid in an Exposed Population
NCT04531176	PHASE4	TERMINATED	EMI-EHP Weight Management and Type 2 Diabetes Pragmatic Trial
NCT05496075	PHASE4	COMPLETED	Orlistat Reduces Uric Acid in Overweight/Obese Patients With Hyperuricemia
NCT05579249	PHASE4	COMPLETED	A Research Study Comparing Wegovy to Other Weight Management Drugs in People Living With Obesity in America
NCT06501326	PHASE4	UNKNOWN	Efficacy and Safety of Liraglutide in the Treatment of Obesity Combined With Metabolism Associated Fatty Liver Disease
NCT00940628	PHASE3	COMPLETED	A Study of Xenical (Orlistat) in Overweight and Obese Adolescents
NCT01755676	PHASE3	COMPLETED	Evaluation of Orlistat as Adjuvant Treatment of Obesity in Adults
NCT02432209	PHASE3	COMPLETED	Improving Reproductive Fitness Through Pretreatment With Lifestyle Modification in Obese Women With Unexplained Infertility
NCT05816343	PHASE2	RECRUITING	Long Term Efficacy and Safety of Orlistat for Type 1 Hyperlipoproteinemia
NCT06818955	PHASE2	NOT_YET_RECRUITING	Orlistat Overcoming Third-generation EGFR-TKI Resistance
NCT00001723	PHASE2	COMPLETED	Safety and Efficacy of Xenical in Children and Adolescents With Obesity-Related Diseases
NCT00156897	PHASE2	COMPLETED	Efficacy and Safety of ATL-962 in Obese Diabetics
NCT00422058	PHASE2	COMPLETED	The Effect of Liraglutide on Body Weight in Obese Subjects Without Diabetes
NCT00704912	PHASE2	COMPLETED	Treatment of Hyperandrogenism Versus Insulin Resistance in Infertile Polycystic Ovary Syndrome (PCOS) Women
NCT01003483	PHASE2	COMPLETED	Metformin Versus Orlistat in Obese Polycystic Ovary Syndrome (PCOS) Patients
NCT01126970	PHASE2	COMPLETED	Double-Blind, Multi-Center, Randomized Study to Assess the Efficacy and Safety of Velneperit (S-2367) and Orlistat Administered Individually or Combined With a Reduced Calorie Diet (RCD) in Obese Subjects
NCT01351753	PHASE2	TERMINATED	Drug Therapy Induced Weight Loss to Improve Blood Vessel Function in Subjects With Obesity
NCT01675154	PHASE2	TERMINATED	Phase 2 Study of Orlistat and SLx-4090 for the Treatment of Type 1 Hyperlipoproteinemia
NCT02069197	PHASE2	UNKNOWN	Ketogenic Diet Treatment of Obesity With Co-morbid Type 2 Diabetes Mellitus and/or Obstructive Sleep Apnea
NCT02503865	PHASE1/PHASE2	COMPLETED	Development of Rational Ways of Medical and Non-medical Treatment Methods for Metabolic Syndrome
NCT02767531	PHASE2	COMPLETED	Orlistat for the Treatment of Type I Hyperlipoproteinemia
NCT01550926	PHASE1	COMPLETED	A Study to Assess the Pharmacologic Equivalence of Two Orlistat Dosage Forms
NCT07326839	Not specified	NOT_YET_RECRUITING	Orlistat and Weight Management for Uric Acid Control in Obese Gout: A RCT
NCT00108524	Not specified	COMPLETED	A Low-Carbohydrate, Ketogenic Diet Versus Orlistat for Weight Loss
NCT00461799	Not specified	COMPLETED	Orlistat Treatment of Crigler-Najjar Disease
NCT00601354	Not specified	COMPLETED	Adding Guided Self-Help Group Therapy to the Alli Weight Loss Program in Treating Binge Eating Disorder
NCT00794963	Not specified	TERMINATED	Aggressive Treatment of Metabolic Syndrome in Patients Receiving Clozapine for Schizophrenia
NCT00829283	Not specified	COMPLETED	Treatment of Obesity and Binge Eating: Behavioral Weight Loss Versus Stepped Care
NCT00991926	Not specified	COMPLETED	Growth Factor/Insulin-like Growth Factor (GH/IGF)-1 Axis in Obese Subjects in Treatment With Orlistat
NCT01170806	Not specified	COMPLETED	Study of Fat Malabsorption by Lipiblock Versus Xenical
NCT01184560	Not specified	COMPLETED	Assess the Additional Weight Loss Effect of Orlistat Used in Combination With Sibutramine
NCT01332448	Not specified	COMPLETED	Meta-analysis of Orlistat Laboratory Data From Placebo-controlled Clinical Trials
NCT01387243	Not specified	COMPLETED	Survey on the Pharmacy Follow-up of Alli Purchasers
NCT01414465	Not specified	COMPLETED	Orlistat Induced Modulation on the Fatty Acid Composition in Obese Females
NCT01719419	Not specified	WITHDRAWN	The Effect of Modified Sham Feeding With Orlistat in Overweight and Obese Subjects
NCT01797757	Not specified	COMPLETED	Comparison of MAG and Fish Oil Efficacy
NCT02529631	Not specified	COMPLETED	RCT to Compare Orlistat and Polyglucosamine for the Management of Overweight and Obesity
NCT03884127	Not specified	UNKNOWN	Ezetimibe and Orlistat Affect the Intestinal Flora of Hyperlipidemia.
NCT06625736	Not specified	COMPLETED	Anti-obesity Effects of Dandelion (Taraxacum Officinale L.)

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.

16 molecules share ≥1 primary target. Top 16 by shared-target count:

Molecule	Source	Status	Shared targets
DRONABINOL	ChEMBL + PubChem	Phase 4 (approved)	ABHD12
LANSOPRAZOLE	ChEMBL + PubChem	Phase 4 (approved)	FASN
PANTOPRAZOLE	ChEMBL + PubChem	Phase 4 (approved)	FASN
RABEPRAZOLE	ChEMBL + PubChem	Phase 4 (approved)	FASN
OMEPRAZOLE	ChEMBL	Phase 4 (approved)	FASN
QUERCETIN	ChEMBL + PubChem	Phase 3 (approved)	PNLIP
EPIGALOCATECHIN GALLATE	ChEMBL	Phase 3	FASN
CANNABIDIOLIC ACID	ChEMBL	Phase 2	DAGLA
CANNABIDIVARIN	ChEMBL	Phase 2	DAGLA
DENIFANSTAT	ChEMBL	Phase 2	FASN
LUTEOLIN	ChEMBL	Phase 2	FASN
RAFOXANIDE	ChEMBL	Phase 2	PNLIP
Cannabidiol	PubChem	Approved	DAGLA
Ezetimibe	PubChem	Approved	PNLIP
Isotretinoin	PubChem	Approved	FASN
methionine	PubChem	Approved	FASN