Explore a selection of our essential drug information below, or:
Identification
- Summary
Orlistat is a reversible inhibitor of gastrointestinal lipases indicated for weight loss and weight maintenance.
- Brand Names
- Alli, Xenical
- Generic Name
- Orlistat
- DrugBank Accession Number
- DB01083
- Background
The global prevalence of obesity is increasing rapidly. Obesity-related complications lead to significant personal and economic burden by reducing quality of life and increasing the cost of healthcare. In some individuals, diet and exercise are insufficient to maintain weight loss, and pharmacological or surgical intervention is required.14
Orlistat is a lipase inhibitor used in the treatment of obesity that works by inhibiting fat-metabolizing enzymes. It was approved by the FDA for use in combination with a reduced-calorie diet in 1999.15 This drug is a generally well-tolerated and effective weight-loss aid and is now available in both over-the-counter16 and prescription preparations, depending on the dosage quantity.15
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Orlistat (DB01083)
- Weight
- Average: 495.7348
Monoisotopic: 495.392373811 - Chemical Formula
- C29H53NO5
- Synonyms
- (-)-Tetrahydrolipstatin
- Orlipastat
- Orlipastatum
- Orlistat
- Tetrahydrolipstatin
- External IDs
- RO 18-0647/002
- RO-18-0647/002
- RO-180647-002
- RO-180647002
Pharmacology
- Indication
Orlistat is indicated for obesity management including weight loss and weight maintenance when used in combination with calorie reduction in overweight and obese adults; this indication applies to both the prescription formulation of 120 mg15 and the over-the-counter formulation of 60 mg.16 Orlistat in the 120 mg prescription formulation is also indicated to reduce the risk of weight regain following weight loss.15
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Prevention of Weight gain •••••••••••• ••••• ••••••• Adjunct therapy in treatment of Weight gain ••• ••• ••••• ••••••• Adjunct therapy in treatment of Weight gain •••••••••••• ••••• ••••••• - Associated Therapies
- Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Orlistat helps with weight reduction and maintenance by inhibiting the absorption of dietary fats via the inhibition of lipase enzymes.9,10
- Mechanism of action
Orlistat is a potent and selective inhibitor of various lipase enzymes responsible for the metabolism of fat. It acts in the gastrointestinal (GI) tract via covalent binding to the serine residues located on the active site of both gastric and pancreatic lipase. When orlistat is taken with food containing fat, it partially inhibits the hydrolysis of triglycerides. This decreases absorption of monoaclglycerides and free fatty acids, contributing to weight maintenance and weight loss.12,15
Target Actions Organism APancreatic triacylglycerol lipase inhibitorHumans ACannabinoid receptor 1 inhibitorHumans AGastric triacylglycerol lipase inhibitorHumans UFatty acid synthase inhibitorHumans - Absorption
The systemic absorption and exposure of orlistat is low, however, systemic absorption of the drug is not required for orlistat activity.18 After an oral dose with 360 mg of radiolabeled orlistat, plasma radioactivity achieved a peak at about 8 hours. Plasma concentrations of unchanged parent drug were close to the lower end of detection limits (<5 ng/mL). In plasma samples of patients taking orlistat, the detection of unchanged drug was sporadic and very low concentrations were detected (<10 ng/mL or 0.02 μM) with no evidence suggesting drug accumulation.15
- Volume of distribution
Volume of distribution cannot be obtained because the absorption of orlistat is minimal. Orlistat is minimally distributed to erythrocytes and is primarily bound to proteins.15
- Protein binding
Orlistat is >99% bound to plasma proteins (mainly lipoproteins and albumin).15
- Metabolism
Orlistat is hydrolyzed in the intestinal wall.17 In a radiolabeled orlistat mass balance study in obese patients, two metabolites were identified. The first metabolite, M1, was the hydrolyzed β-lactone ring product of orlistat. The second metabolite, M3, was produced from M1’s cleavage of the N-formyl leucine side-chain. Both metabolites accounted for about 42% of total plasma radioactivity. Both M1 and M3 are considered pharmacologically inactive.13,15
- Route of elimination
After single oral dose of radiolabled orlistat in both normal weight and obese volunteers fecal excretion of the unabsorbed drug was found to be the major route of elimination with <2% urinary excretion.11,20 Fecal elimination of orlistat is estimated between 95-97%.15 Complete excretion by both routes occurs within in 3 to 5 days.20
- Half-life
The half-life of orlistat of the small amount of absorbed orlistat ranges between 1-2 hours.13,15
- Clearance
Not Available
- Adverse Effects
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The oral LD50 of orlistat is >5000 mg/kg in rats.21 Single orlistat doses of 800 mg and multiple doses of up to 400 mg three times a day for 15 days have been administered to healthy weight and obese subjects without clinically significant adverse findings. In addition, doses of 240 mg three times a day have been given to obese patients for 6 months without a significant adverse effects. Post-marketing reports of overdoses cases indicate no adverse events or adverse events that are similar to those reported with the recommended dose. If a significant overdose with orlistat occurs, the patient should be observed for at least 24 hours. Based on the results of clinical studies, systemic effects caused by orlistat are likely to be rapidly reversible.20
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAcenocoumarol Orlistat may increase the anticoagulant activities of Acenocoumarol. Acetazolamide Orlistat can cause a decrease in the absorption of Acetazolamide resulting in a reduced serum concentration and potentially a decrease in efficacy. Alfacalcidol Orlistat can cause a decrease in the absorption of Alfacalcidol resulting in a reduced serum concentration and potentially a decrease in efficacy. Alitretinoin Orlistat can cause a decrease in the absorption of Alitretinoin resulting in a reduced serum concentration and potentially a decrease in efficacy. alpha-Tocopherol acetate Orlistat can cause a decrease in the absorption of alpha-Tocopherol acetate resulting in a reduced serum concentration and potentially a decrease in efficacy. - Food Interactions
- Take with food. Take with meals or up to 1 hour after a meal. Doses may be skipped for missed meals or fat-free meals.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Alli Capsule 60 mg Oral Glaxosmithkline Dungarvan Limited 2016-09-08 Not applicable EU 
Alli Capsule 60 mg Oral Glaxosmithkline Dungarvan Limited 2016-09-08 Not applicable EU Alli Tablet, chewable 27 mg Oral Glaxosmithkline Dungarvan Limited 2016-09-08 2020-09-03 EU Alli Tablet, chewable 27 mg Oral Glaxosmithkline Dungarvan Limited 2016-09-08 2020-09-03 EU Alli Capsule 60 mg Oral Glaxosmithkline Dungarvan Limited 2016-09-08 Not applicable EU - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Orlistat Capsule 120 mg/1 Oral H2-Pharma, LLC 2022-06-01 Not applicable US 
- Over the Counter Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Alli Capsule 60 mg/1 Oral Aphena Pharma Solutions - Tennessee, LLC 2007-02-07 Not applicable US Alli Capsule 60 mg/1 Oral Haleon US Holdings LLC 2007-02-07 Not applicable US Alli capsule 60mg Capsule 60 mg Oral Glaxosmithkline Consumer Healthcare Ulc 2010-04-07 Not applicable Singapore 
OBELIT 120 CAPSULE 120MG Capsule, gelatin coated 120.00 mg Oral Accord Healthcare, S.L.U. 2017-04-08 Not applicable Singapore XENICAL CAPSULE 120MG Capsule 120 MG Oral DKSH MALAYSIA SDN. BHD. 2005-01-31 Not applicable Singapore
Categories
- ATC Codes
- A08AB01 — Orlistat
- Drug Categories
- Alimentary Tract and Metabolism
- Anti-Obesity Agents
- Antiobesity Preparations, Excl. Diet Products
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (strength unknown)
- Cytochrome P-450 Enzyme Inducers
- Enzyme Inhibitors
- Intestinal Lipase Inhibitor
- Lactones
- Lipase Inhibitors
- Lipid Regulating Agents
- Miscellaneous GI Drugs
- Peripherally Acting Antiobesity Products
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as leucine and derivatives. These are compounds containing leucine or a derivative thereof resulting from reaction of leucine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Leucine and derivatives
- Alternative Parents
- Alpha amino acid esters / N-formyl-alpha amino acids / Fatty acid esters / Dicarboxylic acids and derivatives / Beta propiolactones / Secondary carboxylic acid amides / Oxetanes / Carboxylic acid esters / Oxacyclic compounds / Organopnictogen compounds show 4 more
- Substituents
- Aliphatic heteromonocyclic compound / Alpha-amino acid ester / Beta_propiolactone / Carbonyl group / Carboxamide group / Carboxylic acid ester / Dicarboxylic acid or derivatives / Fatty acid ester / Fatty acyl / Hydrocarbon derivative show 14 more
- Molecular Framework
- Aliphatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
- Rat
- Mouse
Chemical Identifiers
- UNII
- 95M8R751W8
- CAS number
- 96829-58-2
- InChI Key
- AHLBNYSZXLDEJQ-FWEHEUNISA-N
- InChI
- InChI=1S/C29H53NO5/c1-5-7-9-11-12-13-14-15-16-18-24(34-29(33)26(30-22-31)20-23(3)4)21-27-25(28(32)35-27)19-17-10-8-6-2/h22-27H,5-21H2,1-4H3,(H,30,31)/t24-,25-,26-,27-/m0/s1
- IUPAC Name
- (2S)-1-[(2S,3S)-3-hexyl-4-oxooxetan-2-yl]tridecan-2-yl (2S)-2-formamido-4-methylpentanoate
- SMILES
- CCCCCCCCCCC[C@@H](C[C@@H]1OC(=O)[C@H]1CCCCCC)OC(=O)[C@H](CC(C)C)NC=O
References
- Synthesis Reference
Vilmos Keri, "Preparation of orlistat and orlistat crystalline forms." U.S. Patent US20030149095, issued August 07, 2003.
US20030149095- General References
- Torgerson JS, Hauptman J, Boldrin MN, Sjostrom L: XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. 2004 Jan;27(1):155-61. [Article]
- Mancini MC, Halpern A: Pharmacological treatment of obesity. Arq Bras Endocrinol Metabol. 2006 Apr;50(2):377-89. Epub 2006 May 23. [Article]
- Menendez JA, Vellon L, Lupu R: Antitumoral actions of the anti-obesity drug orlistat (XenicalTM) in breast cancer cells: blockade of cell cycle progression, promotion of apoptotic cell death and PEA3-mediated transcriptional repression of Her2/neu (erbB-2) oncogene. Ann Oncol. 2005 Aug;16(8):1253-67. Epub 2005 May 3. [Article]
- Garcia SB, Barros LT, Turatti A, Martinello F, Modiano P, Ribeiro-Silva A, Vespucio MV, Uyemura SA: The anti-obesity agent Orlistat is associated to increase in colonic preneoplastic markers in rats treated with a chemical carcinogen. Cancer Lett. 2006 Aug 28;240(2):221-4. Epub 2005 Dec 27. [Article]
- Drew BS, Dixon AF, Dixon JB: Obesity management: update on orlistat. Vasc Health Risk Manag. 2007;3(6):817-21. [Article]
- Wong NN, Cheng-Lai A: Orlistat. Heart Dis. 2000 Mar-Apr;2(2):174-81. [Article]
- Hvizdos KM, Markham A: Orlistat: a review of its use in the management of obesity. Drugs. 1999 Oct;58(4):743-60. [Article]
- Lucas KH, Kaplan-Machlis B: Orlistat--a novel weight loss therapy. Ann Pharmacother. 2001 Mar;35(3):314-28. [Article]
- Curran MP, Scott LJ: Orlistat: a review of its use in the management of patients with obesity. Drugs. 2004;64(24):2845-64. [Article]
- Ballinger A, Peikin SR: Orlistat: its current status as an anti-obesity drug. Eur J Pharmacol. 2002 Apr 12;440(2-3):109-17. [Article]
- Zhi J, Melia AT, Eggers H, Joly R, Patel IH: Review of limited systemic absorption of orlistat, a lipase inhibitor, in healthy human volunteers. J Clin Pharmacol. 1995 Nov;35(11):1103-8. doi: 10.1002/j.1552-4604.1995.tb04034.x. [Article]
- Guerciolini R: Mode of action of orlistat. Int J Obes Relat Metab Disord. 1997 Jun;21 Suppl 3:S12-23. [Article]
- Zhi J, Melia AT, Funk C, Viger-Chougnet A, Hopfgartner G, Lausecker B, Wang K, Fulton JS, Gabriel L, Mulligan TE: Metabolic profiles of minimally absorbed orlistat in obese/overweight volunteers. J Clin Pharmacol. 1996 Nov;36(11):1006-11. doi: 10.1177/009127009603601104. [Article]
- Williams DM, Nawaz A, Evans M: Drug Therapy in Obesity: A Review of Current and Emerging Treatments. Diabetes Ther. 2020 Jun;11(6):1199-1216. doi: 10.1007/s13300-020-00816-y. Epub 2020 Apr 15. [Article]
- FDA Approved Drug Products: Xenical (orlistat) capsules [Link]
- FDA Approved Drug Products: ALLI (orlistat) oral capsules OTC [Link]
- FDA: Orlistat (marketed as Alli and Xenical) Information [Link]
- NIH StatPearls: Orlistat [Link]
- DailyMed: Alli (orlistat) oral capsule [Link]
- Product monograph: Xenical (orlistat) oral capsules [Link]
- Fagron MSDS: Orlistat [Link]
- FDA Approved Drug Products: Xenical (orlistat) capsules for oral use (Updated 11/2022) [Link]
- External Links
- Human Metabolome Database
- HMDB0015215
- PubChem Compound
- 3034010
- PubChem Substance
- 46508309
- ChemSpider
- 2298564
- BindingDB
- 24567
- 37925
- ChEBI
- 94686
- ChEMBL
- CHEMBL175247
- ZINC
- ZINC000008214635
- Therapeutic Targets Database
- DAP000053
- PharmGKB
- PA164776864
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Orlistat
- FDA label
- Download (82.5 KB)
- MSDS
- Download (114 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Obesity 2 somestatus stop reason just information to hide Not Available Completed Not Available Overweight 1 somestatus stop reason just information to hide Not Available Completed Basic Science Obesity 1 somestatus stop reason just information to hide Not Available Completed Prevention Obesity / Overweight 1 somestatus stop reason just information to hide Not Available Completed Screening Obesity 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- A-S Medication Solutions LLC
- Dispensing Solutions
- Diversified Healthcare Services Inc.
- F Hoffmann La Roche Ltd.
- F Hoffmann-La Roche Ltd.
- GlaxoSmithKline Inc.
- Murfreesboro Pharmaceutical Nursing Supply
- Nucare Pharmaceuticals Inc.
- Physicians Total Care Inc.
- Southwood Pharmaceuticals
- Dosage Forms
Form Route Strength Capsule Oral Capsule Oral 60 mg/1 Tablet Oral 27 MG Tablet, chewable Oral 27 mg Capsule Oral 60 mg Capsule Oral 120.00 mg Tablet Oral 120.000 mg Tablet Oral 60.000 mg Capsule, coated Oral 12000000 mg Tablet Oral 120 MG Capsule, coated Oral 120 mg Capsule Oral 120.000 mg Capsule, coated Oral 60 mg Capsule, gelatin coated Oral 120.00 mg Capsule Oral Powder Not applicable 1 kg/1kg Capsule, liquid filled Oral 120 mg Capsule, liquid filled Oral 12000000 mg Capsule, liquid filled Oral 60 mg Capsule Oral 60.000 mg Capsule Oral 240 mg Capsule Oral 60.00 mg Capsule Oral 120 mg/1 Capsule, gelatin coated Oral 120 mg Capsule, coated Oral 50 % Tablet, soluble Oral 120 mg Capsule Oral 120 mg - Prices
Unit description Cost Unit Xenical 120 mg capsule 4.44USD capsule Alli 60 mg capsule 0.67USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US4598089 No 1986-07-01 2009-12-18 US CA2383036 No 2006-01-10 2020-09-11 Canada 
CA2258095 No 2000-02-22 2018-01-24 Canada US6004996 Yes 1999-12-21 2018-07-06 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 40-50 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223334/ boiling point (°C) 616 https://www.chemicalbook.com/ChemicalProductProperty_US_CB2431985.aspx logP 4.4 https://www.rochecanada.com/PMs/Xenical/Xenical_PM_E.pdf pKa 15 https://www.chemicalbook.com/ChemicalProductProperty_US_CB2431985.aspx - Predicted Properties
Property Value Source Water Solubility 9.19e-05 mg/mL ALOGPS logP 7.61 ALOGPS logP 8.11 Chemaxon logS -6.7 ALOGPS pKa (Strongest Acidic) 12.74 Chemaxon pKa (Strongest Basic) -1.4 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 81.7 Å2 Chemaxon Rotatable Bond Count 23 Chemaxon Refractivity 139.94 m3·mol-1 Chemaxon Polarizability 60.88 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9728 Blood Brain Barrier + 0.5923 Caco-2 permeable - 0.5611 P-glycoprotein substrate Substrate 0.5411 P-glycoprotein inhibitor I Inhibitor 0.6242 P-glycoprotein inhibitor II Inhibitor 0.5301 Renal organic cation transporter Non-inhibitor 0.9097 CYP450 2C9 substrate Non-substrate 0.854 CYP450 2D6 substrate Non-substrate 0.826 CYP450 3A4 substrate Substrate 0.5867 CYP450 1A2 substrate Non-inhibitor 0.8458 CYP450 2C9 inhibitor Non-inhibitor 0.8305 CYP450 2D6 inhibitor Non-inhibitor 0.8869 CYP450 2C19 inhibitor Non-inhibitor 0.7315 CYP450 3A4 inhibitor Non-inhibitor 0.8308 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.907 Ames test Non AMES toxic 0.7333 Carcinogenicity Non-carcinogens 0.8628 Biodegradation Not ready biodegradable 0.7808 Rat acute toxicity 2.3363 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9671 hERG inhibition (predictor II) Non-inhibitor 0.9395
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 271.9793559 predictedDarkChem Lite v0.1.0 [M-H]- 260.2455559 predictedDarkChem Lite v0.1.0 [M-H]- 261.2951559 predictedDarkChem Lite v0.1.0 [M-H]- 238.5065 predictedDeepCCS 1.0 (2019) [M+H]+ 270.0514559 predictedDarkChem Lite v0.1.0 [M+H]+ 259.8375559 predictedDarkChem Lite v0.1.0 [M+H]+ 261.0356559 predictedDarkChem Lite v0.1.0 [M+H]+ 240.9021 predictedDeepCCS 1.0 (2019) [M+Na]+ 269.8558559 predictedDarkChem Lite v0.1.0 [M+Na]+ 260.2085559 predictedDarkChem Lite v0.1.0 [M+Na]+ 246.81459 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Plays an important role in fat metabolism. It preferentially splits the esters of long-chain fatty acids at positions 1 and 3, producing mainly 2-monoacylglycerol and free fatty acids, and shows considerably higher activity against insoluble emulsified substrates than against soluble ones
- Specific Function
- all-trans-retinyl-palmitate hydrolase, all-trans-retinol forming activity
- Gene Name
- PNLIP
- Uniprot ID
- P16233
- Uniprot Name
- Pancreatic triacylglycerol lipase
- Molecular Weight
- 51156.48 Da
References
- Uusitupa M: New aspects in the management of obesity: operation and the impact of lipase inhibitors. Curr Opin Lipidol. 1999 Feb;10(1):3-7. [Article]
- Leonhardt M, Hrupka B, Langhans W: New approaches in the pharmacological treatment of obesity. Eur J Nutr. 1999 Feb;38(1):1-13. [Article]
- Bray GA: Drug treatment of obesity. Baillieres Best Pract Res Clin Endocrinol Metab. 1999 Apr;13(1):131-48. [Article]
- Bray GA: A concise review on the therapeutics of obesity. Nutrition. 2000 Oct;16(10):953-60. [Article]
- Gomis Barbara R: [Pharmacological treatment of obesity]. Rev Med Univ Navarra. 2004 Apr-Jun;48(2):63-5. [Article]
- Drew BS, Dixon AF, Dixon JB: Obesity management: update on orlistat. Vasc Health Risk Manag. 2007;3(6):817-21. [Article]
- Wong NN, Cheng-Lai A: Orlistat. Heart Dis. 2000 Mar-Apr;2(2):174-81. [Article]
- Nelson RH, Miles JM: The use of orlistat in the treatment of obesity, dyslipidaemia and Type 2 diabetes. Expert Opin Pharmacother. 2005 Nov;6(14):2483-91. [Article]
- Heck AM, Yanovski JA, Calis KA: Orlistat, a new lipase inhibitor for the management of obesity. Pharmacotherapy. 2000 Mar;20(3):270-9. [Article]
- Henness S, Perry CM: Orlistat: a review of its use in the management of obesity. Drugs. 2006;66(12):1625-56. [Article]
- Ballinger A, Peikin SR: Orlistat: its current status as an anti-obesity drug. Eur J Pharmacol. 2002 Apr 12;440(2-3):109-17. [Article]
- McNeely W, Benfield P: Orlistat. Drugs. 1998 Aug;56(2):241-9; discussion 250. [Article]
- FDA Approved Drug Products: Xenical (orlistat) capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- G-protein coupled receptor for endogenous cannabinoids (eCBs), including N-arachidonoylethanolamide (also called anandamide or AEA) and 2-arachidonoylglycerol (2-AG), as well as phytocannabinoids, such as delta(9)-tetrahydrocannabinol (THC) (PubMed:15620723, PubMed:27768894, PubMed:27851727). Mediates many cannabinoid-induced effects, acting, among others, on food intake, memory loss, gastrointestinal motility, catalepsy, ambulatory activity, anxiety, chronic pain. Signaling typically involves reduction in cyclic AMP (PubMed:1718258, PubMed:21895628, PubMed:27768894). In the hypothalamus, may have a dual effect on mitochondrial respiration depending upon the agonist dose and possibly upon the cell type. Increases respiration at low doses, while decreases respiration at high doses. At high doses, CNR1 signal transduction involves G-protein alpha-i protein activation and subsequent inhibition of mitochondrial soluble adenylate cyclase, decrease in cyclic AMP concentration, inhibition of protein kinase A (PKA)-dependent phosphorylation of specific subunits of the mitochondrial electron transport system, including NDUFS2. In the hypothalamus, inhibits leptin-induced reactive oxygen species (ROS) formation and mediates cannabinoid-induced increase in SREBF1 and FASN gene expression. In response to cannabinoids, drives the release of orexigenic beta-endorphin, but not that of melanocyte-stimulating hormone alpha/alpha-MSH, from hypothalamic POMC neurons, hence promoting food intake. In the hippocampus, regulates cellular respiration and energy production in response to cannabinoids. Involved in cannabinoid-dependent depolarization-induced suppression of inhibition (DSI), a process in which depolarization of CA1 postsynaptic pyramidal neurons mobilizes eCBs, which retrogradely activate presynaptic CB1 receptors, transiently decreasing GABAergic inhibitory neurotransmission. Also reduces excitatory synaptic transmission (By similarity). In superior cervical ganglions and cerebral vascular smooth muscle cells, inhibits voltage-gated Ca(2+) channels in a constitutive, as well as agonist-dependent manner (PubMed:17895407). In cerebral vascular smooth muscle cells, cannabinoid-induced inhibition of voltage-gated Ca(2+) channels leads to vasodilation and decreased vascular tone (By similarity). Induces leptin production in adipocytes and reduces LRP2-mediated leptin clearance in the kidney, hence participating in hyperleptinemia. In adipose tissue, CNR1 signaling leads to increased expression of SREBF1, ACACA and FASN genes (By similarity). In the liver, activation by endocannabinoids leads to increased de novo lipogenesis and reduced fatty acid catabolism, associated with increased expression of SREBF1/SREBP-1, GCK, ACACA, ACACB and FASN genes. May also affect de novo cholesterol synthesis and HDL-cholesteryl ether uptake. Peripherally modulates energy metabolism (By similarity). In high carbohydrate diet-induced obesity, may decrease the expression of mitochondrial dihydrolipoyl dehydrogenase/DLD in striated muscles, as well as that of selected glucose/ pyruvate metabolic enzymes, hence affecting energy expenditure through mitochondrial metabolism (By similarity). In response to cannabinoid anandamide, elicits a pro-inflammatory response in macrophages, which involves NLRP3 inflammasome activation and IL1B and IL18 secretion (By similarity). In macrophages infiltrating pancreatic islets, this process may participate in the progression of type-2 diabetes and associated loss of pancreatic beta-cells (PubMed:23955712)
- Specific Function
- cannabinoid receptor activity
- Gene Name
- CNR1
- Uniprot ID
- P21554
- Uniprot Name
- Cannabinoid receptor 1
- Molecular Weight
- 52857.365 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Catalyzes the hydrolysis of triacylglycerols to yield free fatty acids, diacylglycerol, monoacylglycerol, and glycerol (PubMed:10358049, PubMed:2243091). Shows a preferential hydrolysis at the sn-3 position of triacylglycerol (PubMed:2243091)
- Specific Function
- lipid binding
- Gene Name
- LIPF
- Uniprot ID
- P07098
- Uniprot Name
- Gastric triacylglycerol lipase
- Molecular Weight
- 45237.375 Da
References
- Lunagariya NA, Patel NK, Jagtap SC, Bhutani KK: Inhibitors of pancreatic lipase: state of the art and clinical perspectives. EXCLI J. 2014 Aug 22;13:897-921. eCollection 2014. [Article]
- Sternby B, Hartmann D, Borgstrom B, Nilsson A: Degree of in vivo inhibition of human gastric and pancreatic lipases by Orlistat (Tetrahydrolipstatin, THL) in the stomach and small intestine. Clin Nutr. 2002 Oct;21(5):395-402. doi: 10.1054/clnu.2002.0565. [Article]
- Heck AM, Yanovski JA, Calis KA: Orlistat, a new lipase inhibitor for the management of obesity. Pharmacotherapy. 2000 Mar;20(3):270-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Fatty acid synthetase is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH. This multifunctional protein contains 7 catalytic activities and a site for the binding of the prosthetic group 4'-phosphopantetheine of the acyl carrier protein ([ACP]) domain
- Specific Function
- (3R)-3-hydroxybutanoyl-[acyl-carrier-protein] hydratase activity
- Gene Name
- FASN
- Uniprot ID
- P49327
- Uniprot Name
- Fatty acid synthase
- Molecular Weight
- 273424.06 Da
References
- Kridel SJ, Axelrod F, Rozenkrantz N, Smith JW: Orlistat is a novel inhibitor of fatty acid synthase with antitumor activity. Cancer Res. 2004 Mar 15;64(6):2070-5. [Article]
- Dowling S, Cox J, Cenedella RJ: Inhibition of fatty acid synthase by Orlistat accelerates gastric tumor cell apoptosis in culture and increases survival rates in gastric tumor bearing mice in vivo. Lipids. 2009 Jun;44(6):489-98. doi: 10.1007/s11745-009-3298-2. Epub 2009 Apr 21. [Article]
- Pemble CW 4th, Johnson LC, Kridel SJ, Lowther WT: Crystal structure of the thioesterase domain of human fatty acid synthase inhibited by Orlistat. Nat Struct Mol Biol. 2007 Aug;14(8):704-9. Epub 2007 Jul 8. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- Curator comments
- Supported by limited in vitro data only.
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Novotna A, Doricakova A, Vrzal R, Maurel P, Pavek P, Dvorak Z: Investigation of Orlistat effects on PXR activation and CYP3A4 expression in primary human hepatocytes and human intestinal LS174T cells. Eur J Pharm Sci. 2010 Oct 9;41(2):276-80. doi: 10.1016/j.ejps.2010.06.019. Epub 2010 Jul 3. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Has primarily calcium-dependent phospholipase and lysophospholipase activities, with a major role in membrane lipid remodeling and biosynthesis of lipid mediators of the inflammatory response (PubMed:10358058, PubMed:14709560, PubMed:16617059, PubMed:17472963, PubMed:18451993, PubMed:27642067, PubMed:7794891, PubMed:8619991, PubMed:8702602, PubMed:9425121). Plays an important role in embryo implantation and parturition through its ability to trigger prostanoid production (By similarity). Preferentially hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity) (PubMed:10358058, PubMed:17472963, PubMed:18451993, PubMed:7794891, PubMed:8619991, PubMed:9425121). Selectively hydrolyzes sn-2 arachidonoyl group from membrane phospholipids, providing the precursor for eicosanoid biosynthesis via the cyclooxygenase pathway (PubMed:10358058, PubMed:17472963, PubMed:18451993, PubMed:7794891, PubMed:9425121). In an alternative pathway of eicosanoid biosynthesis, hydrolyzes sn-2 fatty acyl chain of eicosanoid lysophopholipids to release free bioactive eicosanoids (PubMed:27642067). Hydrolyzes the ester bond of the fatty acyl group attached at sn-1 position of phospholipids (phospholipase A1 activity) only if an ether linkage rather than an ester linkage is present at the sn-2 position. This hydrolysis is not stereospecific (PubMed:7794891). Has calcium-independent phospholipase A2 and lysophospholipase activities in the presence of phosphoinositides (PubMed:12672805). Has O-acyltransferase activity. Catalyzes the transfer of fatty acyl chains from phospholipids to a primary hydroxyl group of glycerol (sn-1 or sn-3), potentially contributing to monoacylglycerol synthesis (PubMed:7794891)
- Specific Function
- calcium ion binding
- Gene Name
- PLA2G4A
- Uniprot ID
- P47712
- Uniprot Name
- Cytosolic phospholipase A2
- Molecular Weight
- 85238.2 Da
References
- Filippatos TD, Gazi IF, Liberopoulos EN, Athyros VG, Elisaf MS, Tselepis AD, Kiortsis DN: The effect of orlistat and fenofibrate, alone or in combination, on small dense LDL and lipoprotein-associated phospholipase A2 in obese patients with metabolic syndrome. Atherosclerosis. 2007 Aug;193(2):428-37. Epub 2006 Sep 5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Fatty acid synthetase is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH. This multifunctional protein contains 7 catalytic activities and a site for the binding of the prosthetic group 4'-phosphopantetheine of the acyl carrier protein ([ACP]) domain
- Specific Function
- (3R)-3-hydroxybutanoyl-[acyl-carrier-protein] hydratase activity
- Gene Name
- FASN
- Uniprot ID
- P49327
- Uniprot Name
- Fatty acid synthase
- Molecular Weight
- 273424.06 Da
References
- Kridel SJ, Axelrod F, Rozenkrantz N, Smith JW: Orlistat is a novel inhibitor of fatty acid synthase with antitumor activity. Cancer Res. 2004 Mar 15;64(6):2070-5. [Article]
- Pemble CW 4th, Johnson LC, Kridel SJ, Lowther WT: Crystal structure of the thioesterase domain of human fatty acid synthase inhibited by Orlistat. Nat Struct Mol Biol. 2007 Aug;14(8):704-9. Epub 2007 Jul 8. [Article]
- Dowling S, Cox J, Cenedella RJ: Inhibition of fatty acid synthase by Orlistat accelerates gastric tumor cell apoptosis in culture and increases survival rates in gastric tumor bearing mice in vivo. Lipids. 2009 Jun;44(6):489-98. doi: 10.1007/s11745-009-3298-2. Epub 2009 Apr 21. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- FDA Approved Drug Products: Xenical (orlistat) capsules [Link]
Drug created at June 13, 2005 13:24 / Updated at August 26, 2024 19:24