Investigational Drug Details
| Drug ID: | D260 |
| Drug Name: | Orlistat |
| Synonyms: | Xenical; (-)-Tetrahydrolipstatin; Orlipastat; Tetrahydrolipstatin |
| Type: | Chemical drug |
| DrugBank ID: | DB01083 |
| DrugBank Description: | 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. 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. This drug is a generally well-tolerated and effective weight-loss aid and is now available in both over-the-counter and prescription preparations, depending on the dosage quantity. |
| PubChem ID: | 3034010 |
| CasNo: | 96829-58-2 |
| Repositioning for NAFLD: | Yes |
| SMILES: | C([C@@H](OC(=O)[C@H](CC(C)C)NC=O)CCCCCCCCCCC)[C@H]1[C@H](CCCCCC)C(=O)O1 |
| Structure: |
|
| InChiKey: | AHLBNYSZXLDEJQ-FWEHEUNISA-N |
| Molecular Weight: | 495.745 |
| DrugBank Targets: | Pancreatic triacylglycerol lipase inhibitor; Gastric triacylglycerol lipase inhibitor; Fatty acid synthase inhibitor |
| DrugBank MoA: | 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. |
| DrugBank Pharmacology: | Orlistat helps with weight reduction and maintenance by inhibiting the absorption of dietary fats via the inhibition of lipase enzymes. |
| DrugBank 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 mg and the over the counter formulation of 60 mg. Orlistat in the 120 mg prescription formulation is also indicated to reduce the risk for weight regain following weight loss. |
| Targets: | FASN inhibitor |
| Therapeutic Category: | Enhance lipid metabolism |
| Clinical Trial Progress: | Phase 4 completed (NCT00160407: Orlistat did not enhance weight loss or improve liver enzymes, measures of insulin resistance, and histopathology. However, subjects who lost >or=5% of body weight over 9 months improved insulin resistance and steatosis, and those subjects who lost >or=9% also achieved improved hepatic histologic changes.) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0236 | ChiCTR-IPR-17012258 | Post-market | Not Recruiting | No Results Available | 05/08/2017 | 21 August 2017 | Details |
| L0985 | NCT00160407 | Phase 4 | Not recruiting | No Results Available | 08/09/2005 | 19 February 2015 | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T20 | Fatty acid synthase | FASN | inhibitor | Enzyme | P49327 | FAS_HUMAN | Details |
| T21 | Diacylglycerol O-acyltransferase 2 | DGAT2 | inhibitor | Enzyme | Q96PD7 | DGAT2_HUMAN | Details |
| T46 | ATP-citrate synthase | ACLY | inhibitor | Transferase | P53396 | ACLY_HUMAN | Details |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A00880 | 34943134 | Antioxidants (Basel) | Hepatoprotective Effect of Bee Bread in Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) Rats: Impact on Oxidative Stress and Inflammation. | Details |
| A01224 | 34822647 | Vet Sci | Protective and Therapeutic Effects of Orlistat on Metabolic Syndrome and Oxidative Stress in High-Fat Diet-Induced Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in Rats: Role on Nrf2 Activation. | Details |
| A01882 | 34574082 | Foods | AGL9: A Novel Hepatoprotective Peptide from the Larvae of Edible Insects Alleviates Obesity-Induced Hepatic Inflammation by Regulating AMPK/Nrf2 Signaling. | Details |
| A04332 | 33664007 | Arab J Gastroenterol | Short-term orlistat therapy improves fatty infiltration indices and liver fibrosis scores in patients with non-alcoholic fatty liver disease and metabolic syndrome. | Details |
| A05930 | 33072533 | Adv Pharm Bull | The Evaluation of Effective Drugs for the Treatment of Non-Alcoholic Fatty Liver Disease: A Systematic Review and Network Meta-Analysis. | Details |
| A08318 | 32153507 | Front Endocrinol (Lausanne) | Effect of Weight Loss Medications on Hepatic Steatosis and Steatohepatitis: A Systematic Review. | Details |
| A08596 | 32045588 | Toxicol Appl Pharmacol | Orlistat delays hepatocarcinogenesis in mice with hepatic co-activation of AKT and c-Met. | Details |
| A08925 | 31935815 | Int J Mol Sci | Antrodan Alleviates High-Fat and High-Fructose Diet-Induced Fatty Liver Disease in C57BL/6 Mice Model via AMPK/Sirt1/SREBP-1c/PPARγ Pathway. | Details |
| A09503 | 31717842 | Nutrients | Efficacy and Mechanism of Polymerized Anthocyanin from Grape-Skin Extract on High-Fat-Diet-Induced Nonalcoholic Fatty Liver Disease. | Details |
| A09731 | 31632457 | Therap Adv Gastroenterol | Effect of orlistat on liver fat content in patients with nonalcoholic fatty liver disease with obesity: assessment using magnetic resonance imaging-derived proton density fat fraction. | Details |
| A12076 | 30611993 | Biomed Pharmacother | Plumbagin reduces obesity and nonalcoholic fatty liver disease induced by fructose in rats through regulation of lipid metabolism, inflammation and oxidative stress. | Details |
| A12313 | 30502373 | Metabolism | Obesity and nonalcoholic fatty liver disease: From pathophysiology to therapeutics. | Details |
| A12474 | 30431378 | Curr Med Res Opin | Severe nonalcoholic steatohepatitis and type 2 diabetes: liver histology after weight loss therapy in a randomized clinical trial. | Details |
| A13421 | 29986142 | J Med Chem | Monoacylglycerol Acyltransferase 2 (MGAT2) Inhibitors for the Treatment of Metabolic Diseases and Nonalcoholic Steatohepatitis (NASH). | Details |
| A13525 | 29930810 | Biomed Rep | Efficacy of orlistat in non-alcoholic fatty liver disease: A systematic review and meta-analysis. | Details |
| A14840 | 29209440 | EPMA J | Efficacy of Fenugreek-based bionanocomposite on renal dysfunction and endogenous intoxication in high-calorie diet-induced obesity rat model-comparative study. | Details |
| A15798 | 28705172 | BMC Endocr Disord | Endocannabinoid receptor blockade reduces alanine aminotransferase in polycystic ovary syndrome independent of weight loss. | Details |
| A16464 | 28372259 | Biomed Pharmacother | Medicinal plants and phytochemicals with anti-obesogenic potentials: A review. | Details |
| A16657 | 28260907 | Ther Clin Risk Manag | Effect of orlistat on periostin, adiponectin, inflammatory markers and ultrasound grades of fatty liver in obese NAFLD patients. | Details |
| A16753 | 28209193 | BMC Complement Altern Med | UP601, a standardized botanical composition composed of Morus alba, Yerba mate and Magnolia officinalis for weight loss. | Details |