Orlistat

Tetrahydrolipstatin. THL. 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. Inhibits also Sn1-specific DAGLA and DAGLB. Inhibits CES2, FASN, PNLIPRP2, ABHD16A, . Orlistat is a saturated derivative of the natural compound Lipstatin, isolated from Streptomyces toxytricini

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

References (27)

Title : Evaluation of drug-drug interactions via inhibition of hydrolases by orlistat, an anti-obesity drug - Hirosawa_2023_Drug.Metab.Dispos__
Author(s) : Hirosawa K , Fukami T , Nakano M , Nakajima M
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , : , 2023
Abstract :
PubMedSearch : Hirosawa_2023_Drug.Metab.Dispos__
PubMedID: 37137721

Title : Identification of cell wall synthesis inhibitors active against Mycobacterium tuberculosis by competitive activity-based protein profiling - Li_2022_Cell.Chem.Biol_29_883
Author(s) : Li M , Patel HV , Cognetta AB, 3rd , Smith TC, 2nd , Mallick I , Cavalier JF , Previti ML , Canaan S , Aldridge BB , Cravatt BF , Seeliger JC
Ref : Cell Chemical Biology , 29 :883 , 2022
Abstract :
PubMedSearch : Li_2022_Cell.Chem.Biol_29_883
PubMedID: 34599873

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 : Lysosomal acid lipase is the major acid retinyl ester hydrolase in cultured human hepatic stellate cells but not essential for retinyl ester degradation - Wagner_2020_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids_1865_158730
Author(s) : Wagner C , Hois V , Pajed L , Pusch LM , Wolinski H , Trauner M , Zimmermann R , Taschler U , Lass A
Ref : Biochimica & Biophysica Acta Molecular & Cellular Biology Lipids , 1865 :158730 , 2020
Abstract :
PubMedSearch : Wagner_2020_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids_1865_158730
PubMedID: 32361002
Gene_locus related to this paper: human-LIPA

Title : Crystal structure of pathogenic Staphylococcus aureus lipase complex with the anti-obesity drug orlistat - Kitadokoro_2020_Sci.Rep_10_5469
Author(s) : Kitadokoro K , Tanaka M , Hikima T , Okuno Y , Yamamoto M , Kamitani S
Ref : Sci Rep , 10 :5469 , 2020
Abstract :
PubMedSearch : Kitadokoro_2020_Sci.Rep_10_5469
PubMedID: 32214208
Gene_locus related to this paper: staau-lipas

Title : The Antimalarial Natural Product Salinipostin A Identifies Essential alpha\/beta Serine Hydrolases Involved in Lipid Metabolism in P. falciparum Parasites - Yoo_2020_Cell.Chem.Biol_27_143
Author(s) : Yoo E , Schulze CJ , Stokes BH , Onguka O , Yeo T , Mok S , Gnadig NF , Zhou Y , Kurita K , Foe IT , Terrell SM , Boucher MJ , Cieplak P , Kumpornsin K , Lee MCS , Linington RG , Long JZ , Uhlemann AC , Weerapana E , Fidock DA , Bogyo M
Ref : Cell Chemical Biology , 27 :143 , 2020
Abstract :
PubMedSearch : Yoo_2020_Cell.Chem.Biol_27_143
PubMedID: 31978322
Gene_locus related to this paper: plaf7-q8ii19 , plafa-a0a143zya4 , plaf7-q8iik5 , plafa-MAL8P1.38 , plafa-PF07.0040 , plafa-PF10.0020 , plafa-PF10.0379 , plafa-PF13.0153

Title : Human leukocytes differentially express endocannabinoid-glycerol lipases and hydrolyze 2-arachidonoyl-glycerol and its metabolites from the 15-lipoxygenase and cyclooxygenase pathways - Turcotte_2019_J.Leukoc.Biol_106_1337
Author(s) : Turcotte C , Dumais E , Archambault AS , Martin C , Blanchet MR , Bissonnette E , Boulet LP , Laviolette M , Di Marzo V , Flamand N
Ref : J Leukoc Biol , 106 :1337 , 2019
Abstract :
PubMedSearch : Turcotte_2019_J.Leukoc.Biol_106_1337
PubMedID: 31556464
Gene_locus related to this paper: human-ABHD6 , human-ABHD12 , human-ABHD16A , human-CES1 , human-LYPLA2 , human-PPT1

Title : Mycolyltransferase from Mycobacterium tuberculosis in covalent complex with tetrahydrolipstatin provides insights into antigen 85 catalysis - Goins_2018_J.Biol.Chem_293_3651
Author(s) : Goins CM , Dajnowicz S , Smith MD , Parks JM , Ronning DR
Ref : Journal of Biological Chemistry , 293 :3651 , 2018
Abstract :
PubMedSearch : Goins_2018_J.Biol.Chem_293_3651
PubMedID: 29352107
Gene_locus related to this paper: myctu-a85c

Title : Characterization of Tetrahydrolipstatin and Stereoderivatives on the Inhibition of Essential Mycobacterium tuberculosis Lipid Esterases - Goins_2018_Biochemistry_57_2383
Author(s) : Goins CM , Sudasinghe TD , Liu X , Wang Y , O'Doherty GA , Ronning DR
Ref : Biochemistry , 57 :2383 , 2018
Abstract :
PubMedSearch : Goins_2018_Biochemistry_57_2383
PubMedID: 29601187
Gene_locus related to this paper: myctu-a85c , myctu-PKS13 , myctu-Rv3802c

Title : Stereochemical Structure Activity Relationship Studies (S-SAR) of Tetrahydrolipstatin - Liu_2018_ACS.Med.Chem.Lett_9_274
Author(s) : Liu X , Wang Y , Duclos RI, Jr. , O'Doherty GA
Ref : ACS Med Chem Lett , 9 :274 , 2018
Abstract :
PubMedSearch : Liu_2018_ACS.Med.Chem.Lett_9_274
PubMedID: 29541373

Title : Lipase inhibitor orlistat prevents hepatitis B virus infection by targeting an early step in the virus life cycle - Esser_2018_Antiviral.Res_151_4
Author(s) : Esser K , Lucifora J , Wettengel J , Singethan K , Glinzer A , Zernecke A , Protzer U
Ref : Antiviral Res , 151 :4 , 2018
Abstract :
PubMedSearch : Esser_2018_Antiviral.Res_151_4
PubMedID: 29309795

Title : Simplified assays of lipolysis enzymes for drug discovery and specificity assessment of known inhibitors - Iglesias_2016_J.Lipid.Res_57_131
Author(s) : Iglesias J , Lamontagne J , Erb H , Gezzar S , Zhao S , Joly E , Truong VL , Skorey K , Crane S , Madiraju SR , Prentki M
Ref : J Lipid Res , 57 :131 , 2016
Abstract :
PubMedSearch : Iglesias_2016_J.Lipid.Res_57_131
PubMedID: 26423520

Title : Targeting Lipid Esterases in Mycobacteria Grown Under Different Physiological Conditions Using Activity-based Profiling with Tetrahydrolipstatin (THL) - Ravindran_2014_Mol.Cell.Proteomics_13_435
Author(s) : Ravindran MS , Rao SP , Cheng X , Shukla A , Cazenave-Gassiot A , Yao SQ , Wenk MR
Ref : Mol Cell Proteomics , 13 :435 , 2014
Abstract :
PubMedSearch : Ravindran_2014_Mol.Cell.Proteomics_13_435
PubMedID: 24345785
Gene_locus related to this paper: myctu-Rv2970c

Title : Biochemical and Pharmacological Characterization of the Human Lymphocyte Antigen B-Associated Transcript 5 (BAT5\/ABHD16A) - Savinainen_2014_PLoS.One_9_e109869
Author(s) : Savinainen JR , Patel JZ , Parkkari T , Navia-Paldanius D , Marjamaa JJ , Laitinen T , Nevalainen T , Laitinen JT
Ref : PLoS ONE , 9 :e109869 , 2014
Abstract :
PubMedSearch : Savinainen_2014_PLoS.One_9_e109869
PubMedID: 25290914
Gene_locus related to this paper: human-ABHD16A , mouse-Abhd16a

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 : Elucidation and chemical modulation of sulfolipid-1 biosynthesis in Mycobacterium tuberculosis - Seeliger_2012_J.Biol.Chem_287_7990
Author(s) : Seeliger JC , Holsclaw CM , Schelle MW , Botyanszki Z , Gilmore SA , Tully SE , Niederweis M , Cravatt BF , Leary JA , Bertozzi CR
Ref : Journal of Biological Chemistry , 287 :7990 , 2012
Abstract :
PubMedSearch : Seeliger_2012_J.Biol.Chem_287_7990
PubMedID: 22194604
Gene_locus related to this paper: myctu-Rv3822

Title : Tetrahydrolipstatin inhibition, functional analyses, and three-dimensional structure of a lipase essential for mycobacterial viability - Crellin_2010_J.Biol.Chem_285_30050
Author(s) : Crellin PK , Vivian JP , Scoble J , Chow FM , West NP , Brammananth R , Proellocks NI , Shahine A , Le Nours J , Wilce MC , Britton WJ , Coppel RL , Rossjohn J , Beddoe T
Ref : Journal of Biological Chemistry , 285 :30050 , 2010
Abstract :
PubMedSearch : Crellin_2010_J.Biol.Chem_285_30050
PubMedID: 20656688
Gene_locus related to this paper: mycs2-a0r619

Title : Asymmetric synthesis of anti-aldol segments via a nonaldol route: synthetic applications to statines and (-)-tetrahydrolipstatin - Ghosh_2009_J.Org.Chem_74_4508
Author(s) : Ghosh AK , Shurrush K , Kulkarni S
Ref : J Org Chem , 74 :4508 , 2009
Abstract :
PubMedSearch : Ghosh_2009_J.Org.Chem_74_4508
PubMedID: 19438217

Title : Trp-107 and trp-253 account for the increased steady state fluorescence that accompanies the conformational change in human pancreatic triglyceride lipase induced by tetrahydrolipstatin and bile salt - Bourbon-Freie_2009_J.Biol.Chem_284_14157
Author(s) : Bourbon-Freie A , Dub RE , Xiao X , Lowe ME
Ref : Journal of Biological Chemistry , 284 :14157 , 2009
Abstract :
PubMedSearch : Bourbon-Freie_2009_J.Biol.Chem_284_14157
PubMedID: 19346257
Gene_locus related to this paper: human-PNLIP

Title : Tetrahydrolipstatin analogues as modulators of endocannabinoid 2-arachidonoylglycerol metabolism - Ortar_2008_J.Med.Chem_51_6970
Author(s) : Ortar G , Bisogno T , Ligresti A , Morera E , Nalli M , Di Marzo V
Ref : Journal of Medicinal Chemistry , 51 :6970 , 2008
Abstract :
PubMedSearch : Ortar_2008_J.Med.Chem_51_6970
PubMedID: 18831576

Title : Further biochemical characterization of human pancreatic lipase-related protein 2 expressed in yeast cells - Eydoux_2007_J.Lipid.Res_48_1539
Author(s) : Eydoux C , De Caro J , Ferrato F , Boullanger P , Lafont D , Laugier R , Carriere F , de Caro A
Ref : J Lipid Res , 48 :1539 , 2007
Abstract :
PubMedSearch : Eydoux_2007_J.Lipid.Res_48_1539
PubMedID: 17401110
Gene_locus related to this paper: human-PNLIPRP2

Title : Mass spectrometric evidence of covalently-bound tetrahydrolipstatin at the catalytic serine of Streptomyces rimosus lipase - Asler_2007_Biochim.Biophys.Acta_1770_163
Author(s) : Asler IL , Zehl M , Kovacic F , Muller R , Abramic M , Allmaier G , Kojic-Prodic B
Ref : Biochimica & Biophysica Acta , 1770 :163 , 2007
Abstract :
PubMedSearch : Asler_2007_Biochim.Biophys.Acta_1770_163
PubMedID: 17137716

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 is a novel inhibitor of fatty acid synthase with antitumor activity - Kridel_2004_Cancer.Res_64_2070
Author(s) : Kridel SJ , Axelrod F , Rozenkrantz N , Smith JW
Ref : Cancer Research , 64 :2070 , 2004
Abstract :
PubMedSearch : Kridel_2004_Cancer.Res_64_2070
PubMedID: 15026345
Gene_locus related to this paper: human-FASN

Title : Inhibition of gastrointestinal lipolysis by Orlistat during digestion of test meals in healthy volunteers - Carriere_2001_Am.J.Physiol.Gastrointest.Liver.Physiol_281_G16
Author(s) : Carriere F , Renou C , Ransac S , Lopez V , De Caro J , Ferrato F , de Caro A , Fleury A , Sanwald-Ducray P , Lengsfeld H , Beglinger C , Hadvary P , Verger R , Laugier R
Ref : American Journal of Physiology Gastrointest Liver Physiol , 281 :G16 , 2001
Abstract :
PubMedSearch : Carriere_2001_Am.J.Physiol.Gastrointest.Liver.Physiol_281_G16
PubMedID: 11408251

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 : Mode of action of orlistat - Guerciolini_1997_Int.J.Obes.Relat.Metab.Disord_21 Suppl 3_S12
Author(s) : Guerciolini R
Ref : Int J Obes Relat Metab Disord , 21 Suppl 3 :S12 , 1997
Abstract :
PubMedSearch : Guerciolini_1997_Int.J.Obes.Relat.Metab.Disord_21 Suppl 3_S12
PubMedID: 9225172