Orlistat
Non-specific lipase inhibitor. Orlistat is a drug designed to treat obesity. Its primary function is preventing the absorption of fats from the human diet, thereby reducing caloric intake. Orlistat works by inhibiting pancreatic lipase, an enzyme that breaks down triglycerides in the intestine. Without this enzyme, triglycerides from the diet are prevented from being hydrolyzed into absorbable free fatty acids and are excreted undigested. The structure of FASN with orlistat shows that it is hydrolysed. Orlistat is a saturated derivative of the natural compound Lipstatin, isolated from Streptomyces toxytricini || Orlistat IC50 human-PNLIP 1 nM
General
Type : Oxooxetan, Lipase inhibitor
Chemical_Nomenclature : [(2S)-1-[(2S,3S)-3-hexyl-4-oxooxetan-2-yl]tridecan-2-yl] (2S)-2-formamido-4-methylpentanoate
Canonical SMILES : CCCCCCCCCCCC(CC1C(C(=O)O1)CCCCCC)OC(=O)C(CC(C)C)NC=O
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 || 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)
InChIKey : AHLBNYSZXLDEJQ-FWEHEUNISA-N || AHLBNYSZXLDEJQ-UHFFFAOYSA-N
Other name(s) : Tetrahydrolipstatin || Orlipastat || Xenical || Alli || (-)-Tetrahydrolipstatin || Orlipastatum || THLP || Lipase Inhibitor || THL || 1-(3-hexyl-4-oxooxetan-2-yl)tridecan-2-yl 2-formamido-4-methylpentanoate || Orlistate || NCGC00095128-01 || Orlistat, 5 || ACMC-20p1ed
MW : 495.73
Formula : C29H53NO5
CAS_number : 96829-58-2
PubChem : 3034010
UniChem : AHLBNYSZXLDEJQ-FWEHEUNISA-N, AHLBNYSZXLDEJQ-UHFFFAOYSA-N
IUPHAR : 5277
Wikipedia : Orlistat
Target
Structures : No structure
Families : Thioesterase, Pancreatic_lipase, Lipase_3
References (27)
| Title : Orlistat Confers Neuroprotection in Traumatic Brain Injury by Modulating Microglial Lipid Metabolism - Yu_2025_Cells_14_1469 |
| Author(s) : Yu C , Ni Y , Xiong Y , Kang H , Jiang Z , Liu Y , Zhang X , Zhao K , Wang S , Gan C , Zhang H |
| Ref : Cells , 14 : , 2025 |
| Abstract : |
| PubMedSearch : Yu_2025_Cells_14_1469 |
| PubMedID: 41002434 |
| Title : Synthetic pancreatic lipase inhibitors in obesity treatment: current updates on in silico design, synthesis, bioactivity, and SAR - Jagtap_2025_RSC.Med.Chem__ |
| Author(s) : Jagtap UA , Paul AT |
| Ref : RSC Med Chem , : , 2025 |
| Abstract : |
| PubMedSearch : Jagtap_2025_RSC.Med.Chem__ |
| PubMedID: 41058933 |
| Gene_locus related to this paper: human-PNLIP , pig-1plip |
| Title : Synthetic pancreatic lipase inhibitors in obesity treatment: current updates on in silico design, synthesis, bioactivity, and SAR - Jagtap_2025_RSC.Med.Chem__ |
| Author(s) : Jagtap UA , Paul AT |
| Ref : RSC Med Chem , : , 2025 |
| Abstract : |
| PubMedSearch : Jagtap_2025_RSC.Med.Chem__ |
| PubMedID: 41058933 |
| Gene_locus related to this paper: human-PNLIP , pig-1plip |
| Title : Orlistat Confers Neuroprotection in Traumatic Brain Injury by Modulating Microglial Lipid Metabolism - Yu_2025_Cells_14_1469 |
| Author(s) : Yu C , Ni Y , Xiong Y , Kang H , Jiang Z , Liu Y , Zhang X , Zhao K , Wang S , Gan C , Zhang H |
| Ref : Cells , 14 : , 2025 |
| Abstract : |
| PubMedSearch : Yu_2025_Cells_14_1469 |
| PubMedID: 41002434 |
| Title : Synthetic pancreatic lipase inhibitors in obesity treatment: current updates on in silico design, synthesis, bioactivity, and SAR - Jagtap_2025_RSC.Med.Chem__ |
| Author(s) : Jagtap UA , Paul AT |
| Ref : RSC Med Chem , : , 2025 |
| Abstract : |
| PubMedSearch : Jagtap_2025_RSC.Med.Chem__ |
| PubMedID: 41058933 |
| Gene_locus related to this paper: human-PNLIP , pig-1plip |
| Title : Orlistat Confers Neuroprotection in Traumatic Brain Injury by Modulating Microglial Lipid Metabolism - Yu_2025_Cells_14_1469 |
| Author(s) : Yu C , Ni Y , Xiong Y , Kang H , Jiang Z , Liu Y , Zhang X , Zhao K , Wang S , Gan C , Zhang H |
| Ref : Cells , 14 : , 2025 |
| Abstract : |
| PubMedSearch : Yu_2025_Cells_14_1469 |
| PubMedID: 41002434 |
| Title : Antilipase and antioxidant activities of topiramate-phenolic acid conjugates: Computational modelling, synthesis, and in-vitro investigations - Padhy_2024_Biochem.Biophys.Res.Commun_745_151200 |
| Author(s) : Padhy I , Banerjee B , Sharma T , Achary PGR , Singh N , Chandra A |
| Ref : Biochemical & Biophysical Research Communications , 745 :151200 , 2024 |
| Abstract : |
| PubMedSearch : Padhy_2024_Biochem.Biophys.Res.Commun_745_151200 |
| PubMedID: 39729676 |
| Gene_locus related to this paper: human-PNLIP |
| Title : Antilipase and antioxidant activities of topiramate-phenolic acid conjugates: Computational modelling, synthesis, and in-vitro investigations - Padhy_2024_Biochem.Biophys.Res.Commun_745_151200 |
| Author(s) : Padhy I , Banerjee B , Sharma T , Achary PGR , Singh N , Chandra A |
| Ref : Biochemical & Biophysical Research Communications , 745 :151200 , 2024 |
| Abstract : |
| PubMedSearch : Padhy_2024_Biochem.Biophys.Res.Commun_745_151200 |
| PubMedID: 39729676 |
| Gene_locus related to this paper: human-PNLIP |
| Title : Antilipase and antioxidant activities of topiramate-phenolic acid conjugates: Computational modelling, synthesis, and in-vitro investigations - Padhy_2024_Biochem.Biophys.Res.Commun_745_151200 |
| Author(s) : Padhy I , Banerjee B , Sharma T , Achary PGR , Singh N , Chandra A |
| Ref : Biochemical & Biophysical Research Communications , 745 :151200 , 2024 |
| Abstract : |
| PubMedSearch : Padhy_2024_Biochem.Biophys.Res.Commun_745_151200 |
| PubMedID: 39729676 |
| Gene_locus related to this paper: human-PNLIP |
| Title : Total Synthesis of Tetrahydrolipstatin, Its Derivatives, and Evaluation of Their Ability to Potentiate Multiple Antibiotic Classes against Mycobacterium Species - Khan_2021_ACS.Infect.Dis_7_2876 |
| Author(s) : Khan SS , Sudasinghe TD , Landgraf AD , Ronning DR , Sucheck SJ |
| Ref : ACS Infect Dis , 7 :2876 , 2021 |
| Abstract : |
| PubMedSearch : Khan_2021_ACS.Infect.Dis_7_2876 |
| PubMedID: 34478259 |
| Gene_locus related to this paper: myctu-a85c |
| Title : Total Synthesis of Tetrahydrolipstatin, Its Derivatives, and Evaluation of Their Ability to Potentiate Multiple Antibiotic Classes against Mycobacterium Species - Khan_2021_ACS.Infect.Dis_7_2876 |
| Author(s) : Khan SS , Sudasinghe TD , Landgraf AD , Ronning DR , Sucheck SJ |
| Ref : ACS Infect Dis , 7 :2876 , 2021 |
| Abstract : |
| PubMedSearch : Khan_2021_ACS.Infect.Dis_7_2876 |
| PubMedID: 34478259 |
| Gene_locus related to this paper: myctu-a85c |
| Title : Total Synthesis of Tetrahydrolipstatin, Its Derivatives, and Evaluation of Their Ability to Potentiate Multiple Antibiotic Classes against Mycobacterium Species - Khan_2021_ACS.Infect.Dis_7_2876 |
| Author(s) : Khan SS , Sudasinghe TD , Landgraf AD , Ronning DR , Sucheck SJ |
| Ref : ACS Infect Dis , 7 :2876 , 2021 |
| Abstract : |
| PubMedSearch : Khan_2021_ACS.Infect.Dis_7_2876 |
| PubMedID: 34478259 |
| Gene_locus related to this paper: myctu-a85c |
| Title : Structure activity relationship studies on chemically non-reactive glycine sulfonamide inhibitors of diacylglycerol lipase - Chupak_2016_Bioorg.Med.Chem_24_1455 |
| Author(s) : Chupak LS , Zheng X , Hu S , Huang Y , Ding M , Lewis MA , Westphal RS , Blat Y , McClure A , Gentles RG |
| Ref : Bioorganic & Medicinal Chemistry , 24 :1455 , 2016 |
| Abstract : |
| PubMedSearch : Chupak_2016_Bioorg.Med.Chem_24_1455 |
| PubMedID: 26917221 |
| Gene_locus related to this paper: human-DAGLA |
| Title : Structure activity relationship studies on chemically non-reactive glycine sulfonamide inhibitors of diacylglycerol lipase - Chupak_2016_Bioorg.Med.Chem_24_1455 |
| Author(s) : Chupak LS , Zheng X , Hu S , Huang Y , Ding M , Lewis MA , Westphal RS , Blat Y , McClure A , Gentles RG |
| Ref : Bioorganic & Medicinal Chemistry , 24 :1455 , 2016 |
| Abstract : |
| PubMedSearch : Chupak_2016_Bioorg.Med.Chem_24_1455 |
| PubMedID: 26917221 |
| Gene_locus related to this paper: human-DAGLA |
| Title : Structure activity relationship studies on chemically non-reactive glycine sulfonamide inhibitors of diacylglycerol lipase - Chupak_2016_Bioorg.Med.Chem_24_1455 |
| Author(s) : Chupak LS , Zheng X , Hu S , Huang Y , Ding M , Lewis MA , Westphal RS , Blat Y , McClure A , Gentles RG |
| Ref : Bioorganic & Medicinal Chemistry , 24 :1455 , 2016 |
| Abstract : |
| PubMedSearch : Chupak_2016_Bioorg.Med.Chem_24_1455 |
| PubMedID: 26917221 |
| Gene_locus related to this paper: human-DAGLA |
| Title : Mechanism of Orlistat Hydrolysis by the Thioesterase of Human Fatty Acid Synthase - Fako_2014_ACS.Catal_4_3444 |
| Author(s) : Fako VE , Zhang JT , Liu JY |
| Ref : ACS Catal , 4 :3444 , 2014 |
| Abstract : |
| PubMedSearch : Fako_2014_ACS.Catal_4_3444 |
| PubMedID: 25309810 |
| Gene_locus related to this paper: human-FASN |
| Title : Mechanism of Orlistat Hydrolysis by the Thioesterase of Human Fatty Acid Synthase - Fako_2014_ACS.Catal_4_3444 |
| Author(s) : Fako VE , Zhang JT , Liu JY |
| Ref : ACS Catal , 4 :3444 , 2014 |
| Abstract : |
| PubMedSearch : Fako_2014_ACS.Catal_4_3444 |
| PubMedID: 25309810 |
| Gene_locus related to this paper: human-FASN |
| Title : Mechanism of Orlistat Hydrolysis by the Thioesterase of Human Fatty Acid Synthase - Fako_2014_ACS.Catal_4_3444 |
| Author(s) : Fako VE , Zhang JT , Liu JY |
| Ref : ACS Catal , 4 :3444 , 2014 |
| Abstract : |
| PubMedSearch : Fako_2014_ACS.Catal_4_3444 |
| PubMedID: 25309810 |
| Gene_locus related to this paper: human-FASN |
| Title : Carboxylesterase-2 is a highly sensitive target of the antiobesity agent orlistat with profound implications in the activation of anticancer prodrugs - Xiao_2013_Biochem.Pharmacol_85_439 |
| Author(s) : Xiao D , Shi D , Yang D , Barthel B , Koch TH , Yan B |
| Ref : Biochemical Pharmacology , 85 :439 , 2013 |
| Abstract : |
| PubMedSearch : Xiao_2013_Biochem.Pharmacol_85_439 |
| PubMedID: 23228697 |
| Gene_locus related to this paper: human-CES2 |
| Title : Carboxylesterase-2 is a highly sensitive target of the antiobesity agent orlistat with profound implications in the activation of anticancer prodrugs - Xiao_2013_Biochem.Pharmacol_85_439 |
| Author(s) : Xiao D , Shi D , Yang D , Barthel B , Koch TH , Yan B |
| Ref : Biochemical Pharmacology , 85 :439 , 2013 |
| Abstract : |
| PubMedSearch : Xiao_2013_Biochem.Pharmacol_85_439 |
| PubMedID: 23228697 |
| Gene_locus related to this paper: human-CES2 |
| Title : Carboxylesterase-2 is a highly sensitive target of the antiobesity agent orlistat with profound implications in the activation of anticancer prodrugs - Xiao_2013_Biochem.Pharmacol_85_439 |
| Author(s) : Xiao D , Shi D , Yang D , Barthel B , Koch TH , Yan B |
| Ref : Biochemical Pharmacology , 85 :439 , 2013 |
| Abstract : |
| PubMedSearch : Xiao_2013_Biochem.Pharmacol_85_439 |
| PubMedID: 23228697 |
| Gene_locus related to this paper: human-CES2 |
| Title : Crystal structure of the thioesterase domain of human fatty acid synthase inhibited by Orlistat - Pemble_2007_Nat.Struct.Mol.Biol_14_704 |
| Author(s) : Pemble CWt , Johnson LC , Kridel SJ , Lowther WT |
| Ref : Nat Struct Mol Biol , 14 :704 , 2007 |
| Abstract : |
| PubMedSearch : Pemble_2007_Nat.Struct.Mol.Biol_14_704 |
| PubMedID: 17618296 |
| Gene_locus related to this paper: human-FASN |
| Title : Crystal structure of the thioesterase domain of human fatty acid synthase inhibited by Orlistat - Pemble_2007_Nat.Struct.Mol.Biol_14_704 |
| Author(s) : Pemble CWt , Johnson LC , Kridel SJ , Lowther WT |
| Ref : Nat Struct Mol Biol , 14 :704 , 2007 |
| Abstract : |
| PubMedSearch : Pemble_2007_Nat.Struct.Mol.Biol_14_704 |
| PubMedID: 17618296 |
| Gene_locus related to this paper: human-FASN |
| Title : Crystal structure of the thioesterase domain of human fatty acid synthase inhibited by Orlistat - Pemble_2007_Nat.Struct.Mol.Biol_14_704 |
| Author(s) : Pemble CWt , Johnson LC , Kridel SJ , Lowther WT |
| Ref : Nat Struct Mol Biol , 14 :704 , 2007 |
| Abstract : |
| PubMedSearch : Pemble_2007_Nat.Struct.Mol.Biol_14_704 |
| PubMedID: 17618296 |
| Gene_locus related to this paper: human-FASN |
| Title : Orlistat F Hoffmann-La Roche Ltd - Malone_1998_IDrugs_1_232 |
| Author(s) : Malone M |
| Ref : IDrugs , 1 :232 , 1998 |
| Abstract : |
| PubMedSearch : Malone_1998_IDrugs_1_232 |
| PubMedID: 18465537 |
| Title : Orlistat F Hoffmann-La Roche Ltd - Malone_1998_IDrugs_1_232 |
| Author(s) : Malone M |
| Ref : IDrugs , 1 :232 , 1998 |
| Abstract : |
| PubMedSearch : Malone_1998_IDrugs_1_232 |
| PubMedID: 18465537 |
| Title : Orlistat F Hoffmann-La Roche Ltd - Malone_1998_IDrugs_1_232 |
| Author(s) : Malone M |
| Ref : IDrugs , 1 :232 , 1998 |
| Abstract : |
| PubMedSearch : Malone_1998_IDrugs_1_232 |
| PubMedID: 18465537 |