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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:51 UTC
Update Date2020-02-26 21:41:11 UTC
HMDB IDHMDB0015215
Secondary Accession Numbers
  • HMDB15215
Metabolite Identification
Common NameOrlistat
DescriptionOrlistat 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.
Structure
Data?1582753271
Synonyms
ValueSource
(-)-TetrahydrolipostatinChEBI
(2S)-2-Formamido-4-methylpentanoic acid [(2S)-1-[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]tridecan-2-yl] esterChEBI
AlliChEBI
N-Formyl-L-leucine (1S)-1-{[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl}dodecyl esterChEBI
OrlipastatChEBI
OrlistatumChEBI
Ro-18-0647ChEBI
XenicalChEBI
(2S)-2-Formamido-4-methylpentanoate [(2S)-1-[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]tridecan-2-yl] esterGenerator
(-)-TetrahydrolipstatinHMDB
TetrahydrolipstatinHMDB
Roche brand OF orlistatHMDB
THLPHMDB
1-((3-Hexyl-4-oxo-2-oxetanyl)methyl)dodecyl-2-formamido-4-methylvalerateHMDB
GlaxoSmithKline brand OF orlistatHMDB
Hoffmann-la roche brand OF orlistatHMDB
TetrahydrolipastatinHMDB
Chemical FormulaC29H53NO5
Average Molecular Weight495.7348
Monoisotopic Molecular Weight495.392373811
IUPAC Name(2S)-1-[(2S,3S)-3-hexyl-4-oxooxetan-2-yl]tridecan-2-yl (2S)-2-formamido-4-methylpentanoate
Traditional Nameorlistat
CAS Registry Number96829-58-2
SMILES
CCCCCCCCCCC[C@@H](C[C@@H]1OC(=O)[C@H]1CCCCCC)OC(=O)[C@H](CC(C)C)NC=O
InChI Identifier
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 KeyAHLBNYSZXLDEJQ-FWEHEUNISA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as leucine and derivatives. Leucine and derivatives 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.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentLeucine and derivatives
Alternative Parents
Substituents
  • Leucine or derivatives
  • Alpha-amino acid ester
  • N-formyl-alpha amino acid or derivatives
  • N-formyl-alpha-amino acid
  • Fatty acid ester
  • Dicarboxylic acid or derivatives
  • Fatty acyl
  • Beta_propiolactone
  • Carboxamide group
  • Carboxylic acid ester
  • Secondary carboxylic acid amide
  • Oxetane
  • Lactone
  • Oxacycle
  • Organoheterocyclic compound
  • Organic nitrogen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Carbonyl group
  • Organic oxygen compound
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External DescriptorsNot Available
Ontology
Disposition

Biological location:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility9.2e-05 g/LNot Available
LogP8.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility9.2e-05 g/LALOGPS
logP7.61ALOGPS
logP8.11ChemAxon
logS-6.7ALOGPS
pKa (Strongest Acidic)12.74ChemAxon
pKa (Strongest Basic)-0.91ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area81.7 ŲChemAxon
Rotatable Bond Count23ChemAxon
Refractivity139.94 m³·mol⁻¹ChemAxon
Polarizability61.12 ųChemAxon
Number of Rings1ChemAxon
BioavailabilityNoChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-03di-2902200000-dfdc46fddbbd1d2170e0Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-001i-0000190000-0f2b7ec7f6bc7f95ba46Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-001i-0000390000-65e16678dbfdcc1c64fdSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-00di-0001190000-27c5d161a5754e1434f4Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-00di-0001190000-27c5d161a5754e1434f4Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0pb9-0971000000-b771a74c99af15873a47Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0pb9-0971000000-b771a74c99af15873a47Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014j-0201900000-f738d9eb60da2cb3f8b2Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0btd-4903200000-880d8bcbe0e86c1dedeeSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4m-9300100000-59ee07367048664d1aeaSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-2103900000-12eb6aa4152fd723fd4cSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0zfu-7508900000-d827e3d71bdc755b28a0Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-002f-9315000000-4c6b30daf1a2bd6ffaf8Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01083 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01083 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01083
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID2298564
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkOrlistat
METLIN IDNot Available
PubChem Compound3034010
PDB IDNot Available
ChEBI ID94686
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB ID
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Hvizdos KM, Markham A: Orlistat: a review of its use in the management of obesity. Drugs. 1999 Oct;58(4):743-60. [PubMed:10551441 ]
  2. Lucas KH, Kaplan-Machlis B: Orlistat--a novel weight loss therapy. Ann Pharmacother. 2001 Mar;35(3):314-28. [PubMed:11261530 ]
  3. Wong NN, Cheng-Lai A: Orlistat. Heart Dis. 2000 Mar-Apr;2(2):174-81. [PubMed:11728255 ]
  4. Ballinger A, Peikin SR: Orlistat: its current status as an anti-obesity drug. Eur J Pharmacol. 2002 Apr 12;440(2-3):109-17. [PubMed:12007529 ]
  5. 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. [PubMed:14693982 ]
  6. Curran MP, Scott LJ: Orlistat: a review of its use in the management of patients with obesity. Drugs. 2004;64(24):2845-64. [PubMed:15563254 ]
  7. 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. [PubMed:15870086 ]
  8. 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. [PubMed:16377080 ]
  9. Mancini MC, Halpern A: Pharmacological treatment of obesity. Arq Bras Endocrinol Metabol. 2006 Apr;50(2):377-89. Epub 2006 May 23. [PubMed:16767304 ]
  10. Drew BS, Dixon AF, Dixon JB: Obesity management: update on orlistat. Vasc Health Risk Manag. 2007;3(6):817-21. [PubMed:18200802 ]

Enzymes

General function:
Involved in transferase activity
Specific function:
Fatty acid synthetase catalyzes the formation of long-chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH. This multifunctional protein has 7 catalytic activities and an acyl carrier protein.
Gene Name:
FASN
Uniprot ID:
P49327
Molecular weight:
273424.06
References
  1. 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. [PubMed:15026345 ]
  2. Knowles LM, Axelrod F, Browne CD, Smith JW: A fatty acid synthase blockade induces tumor cell-cycle arrest by down-regulating Skp2. J Biol Chem. 2004 Jul 16;279(29):30540-5. Epub 2004 May 11. [PubMed:15138278 ]
  3. 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. [PubMed:15870086 ]
  4. Kremer L, de Chastellier C, Dobson G, Gibson KJ, Bifani P, Balor S, Gorvel JP, Locht C, Minnikin DE, Besra GS: Identification and structural characterization of an unusual mycobacterial monomeromycolyl-diacylglycerol. Mol Microbiol. 2005 Aug;57(4):1113-26. [PubMed:16091048 ]
  5. Purohit VC, Richardson RD, Smith JW, Romo D: Practical, catalytic, asymmetric synthesis of beta-lactones via a sequential ketene dimerization/hydrogenation process: inhibitors of the thioesterase domain of fatty acid synthase. J Org Chem. 2006 Jun 9;71(12):4549-58. [PubMed:16749788 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
General function:
Involved in metabolic process
Specific function:
Selectively hydrolyzes arachidonyl phospholipids in the sn-2 position releasing arachidonic acid. Together with its lysophospholipid activity, it is implicated in the initiation of the inflammatory response.
Gene Name:
PLA2G4A
Uniprot ID:
P47712
Molecular weight:
85210.19
References
  1. 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. [PubMed:16911813 ]
General function:
Involved in catalytic activity
Specific function:
Not Available
Gene Name:
PNLIP
Uniprot ID:
P16233
Molecular weight:
51156.48
References
  1. 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. [PubMed:10095983 ]
  2. Leonhardt M, Hrupka B, Langhans W: New approaches in the pharmacological treatment of obesity. Eur J Nutr. 1999 Feb;38(1):1-13. [PubMed:10338682 ]
  3. Bray GA: Drug treatment of obesity. Baillieres Best Pract Res Clin Endocrinol Metab. 1999 Apr;13(1):131-48. [PubMed:10932681 ]
  4. Bray GA: A concise review on the therapeutics of obesity. Nutrition. 2000 Oct;16(10):953-60. [PubMed:11054601 ]
  5. Gomis Barbara R: [Pharmacological treatment of obesity]. Rev Med Univ Navarra. 2004 Apr-Jun;48(2):63-5. [PubMed:15382615 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  7. Drew BS, Dixon AF, Dixon JB: Obesity management: update on orlistat. Vasc Health Risk Manag. 2007;3(6):817-21. [PubMed:18200802 ]
  8. Wong NN, Cheng-Lai A: Orlistat. Heart Dis. 2000 Mar-Apr;2(2):174-81. [PubMed:11728255 ]
  9. 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. [PubMed:16259579 ]
  10. Heck AM, Yanovski JA, Calis KA: Orlistat, a new lipase inhibitor for the management of obesity. Pharmacotherapy. 2000 Mar;20(3):270-9. [PubMed:10730683 ]
  11. Henness S, Perry CM: Orlistat: a review of its use in the management of obesity. Drugs. 2006;66(12):1625-56. [PubMed:16956313 ]
  12. Ballinger A, Peikin SR: Orlistat: its current status as an anti-obesity drug. Eur J Pharmacol. 2002 Apr 12;440(2-3):109-17. [PubMed:12007529 ]
  13. McNeely W, Benfield P: Orlistat. Drugs. 1998 Aug;56(2):241-9; discussion 250. [PubMed:9711448 ]
General function:
Involved in lipid metabolic process
Specific function:
Not Available
Gene Name:
LIPF
Uniprot ID:
P07098
Molecular weight:
45237.375
References
  1. Drew BS, Dixon AF, Dixon JB: Obesity management: update on orlistat. Vasc Health Risk Manag. 2007;3(6):817-21. [PubMed:18200802 ]
  2. Wong NN, Cheng-Lai A: Orlistat. Heart Dis. 2000 Mar-Apr;2(2):174-81. [PubMed:11728255 ]
  3. Bray GA: Lifestyle and pharmacological approaches to weight loss: efficacy and safety. J Clin Endocrinol Metab. 2008 Nov;93(11 Suppl 1):S81-8. doi: 10.1210/jc.2008-1294. [PubMed:18987274 ]
  4. 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. [PubMed:16259579 ]
  5. Heck AM, Yanovski JA, Calis KA: Orlistat, a new lipase inhibitor for the management of obesity. Pharmacotherapy. 2000 Mar;20(3):270-9. [PubMed:10730683 ]
  6. Henness S, Perry CM: Orlistat: a review of its use in the management of obesity. Drugs. 2006;66(12):1625-56. [PubMed:16956313 ]
  7. Curran MP, Scott LJ: Orlistat: a review of its use in the management of patients with obesity. Drugs. 2004;64(24):2845-64. [PubMed:15563254 ]
  8. Ballinger A, Peikin SR: Orlistat: its current status as an anti-obesity drug. Eur J Pharmacol. 2002 Apr 12;440(2-3):109-17. [PubMed:12007529 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
References
  1. 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. [PubMed:20599501 ]