(2S)-1-[(2S,3S)-3-hexyl-4-oxooxetan-2-yl]tridecan-2-yl (2S)-2-formamido-4-methylpentanoate

• ChemBase ID: 954
• Molecular Formular: C29H53NO5
• Molecular Mass: 495.73482
• Monoisotopic Mass: 495.3923738
• SMILES: O1[C@H]([C@H](CCCCCC)C1=O)C[C@@H](OC(=O)[C@@H](NC=O)CC(C)C)CCCCCCCCCCC
• Canonical SMILES: CCCCCCCCCCC[C@@H](C[C@@H]1OC(=O)[C@H]1CCCCCC)OC(=O)[C@H](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
• InChIKey: AHLBNYSZXLDEJQ-FWEHEUNISA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (2S)-1-[(2S,3S)-3-hexyl-4-oxooxetan-2-yl]tridecan-2-yl (2S)-2-formamido-4-methylpentanoate
• IUPAC Traditional name: orlistat
• Brand Name: Xenical; Alli
• Synonyms: (-)-Tetrahydrolipstatin; Orlipastatum [INN-Latin]; Tetrahydrolipstatin; Orlipastat; orlistat; Orlistat; N-Formyl-L-leucine (1S)-1-[[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]dodecyl ester; Ro-18-0647; Orlistat; Ro 18-0647/002; S,S,S,S-Orlistat; Alli; Xenical

Database IDs

• CAS Number: 96829-58-2
• MDL Number: MFCD05662360
• PubChem SID: 46508309; 24724564; 160964417
• PubChem CID: 3034010

CALCULATED PROPERTIES

JChem

• Acid pKa: 12.743767
• H Acceptors: 3
• H Donor: 1
• LogD (pH = 5.5): 8.106578
• LogD (pH = 7.4): 8.106576
• Log P: 8.106578
• Molar Refractivity: 139.9443 cm^3
• Polarizability: 56.149376 Å^3
• Polar Surface Area: 81.7 Å^2
• Rotatable Bonds: 23
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 7.61
• LOG S: -6.73
• Solubility (Water): 9.19e-05 g/l

PROPERTIES

Physical Property

• Solubility: Acetone; Chloroform; DMSO: soluble19 mg/mL; Ethyl Acetate; Methanol; Practically insoluble
• Apperance: Off-White to White Solid; white solid
• Melting Point: <50 °C; 42-44°C
• Hydrophobicity(logP): 8.6

Safety Information

• Storage Condition: -20°C; -20°C Freezer
• German water hazard class: 3
• Personal Protective Equipment: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter
• Storage Temperature: 2-8°C

Pharmacology Properties

• Gene Information: human ... PNLIP(5406)

Product Information

• Purity: ≥98%
• Salt Data: Free Base
• Empirical Formula (Hill Notation): C29H53NO5

DETAILS

DrugBank - DB01083

• Drug Groups: approved; investigational
• Description: 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.
• Indication: For obesity management including weight loss and weight maintenance when used in conjunction with a reduced-calorie diet. Also used to reduce the risk for weight regain after prior weight loss. Use of orlistat is pending revision due to reports of liver-related adverse events.
• Pharmacology: Orlistat is a lipase inhibitor for obesity management that acts by; inhibiting the absorption of dietary fats. At the recommended; therapeutic dose of 120 mg three times a day, orlistat inhibits; dietary fat absorption by approximately 30%. It works by inhibiting pancreatic lipase, an enzyme that breaks down fat in the intestine. Without this enzyme, fat from the diet is excreted; undigested and not absorbed by the body. Because some vitamins are fat soluble, the effect of orlistat is to reduce their body; absorption. Therefore the drug should only be taken in conjuction with fatty meals, and a multivitamin tablet containing these vitamins (D E K and beta-carotene) should be taken once a day, at least 2 hours before or after taking the drug. In the March 15, 2004 issue of Cancer Research, [1] Steven J. Kridel et al. state that orlistat may also inhibit growth of prostate cancer, and in theory may be useful in treating other cancers, by interfering with the metabolism of fats.
• Toxicity: The results of a massive overdose of Xenical are unknown, although the drug seems relatively harmless.
• Affected Organisms: Humans and other mammals
• Biotransformation: Metabolized primarily within the gastrointestinal wall forming relatively inactive metabolites. Metabolites M1 (4-member lactone ring hydrolyzed) and M3 (M1 with N-formyl leucine moiety cleaved) accounted for approximately 42% of total radioactivity in plasma. M1 and M3 have an open beta-lactone ring and extremely weak lipase inhibitory activity (1000- and 2500-fold less than orlistat, respectively).
• Absorption: Systemic absorption of orlistat is minimal, however systemic absorption of the drug is not needed for activity.
• Half Life: 1 to 2 hours.
• Protein Binding: >99% bound to plasma proteins (lipoproteins and albumin were major binding proteins).
• Elimination: Following a single oral dose of 360 mg 14C-orlistat in both normal weight and obese subjects, fecal excretion of the unabsorbed drug was found to be the major route of elimination. Orlistat and its M1 and M3 metabolites were also subject to biliary excretion.
• 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. [Pubmed] ; Mancini MC, Halpern A: Pharmacological treatment of obesity. Arq Bras Endocrinol Metabol. 2006 Apr;50(2):377-89. Epub 2006 May 23. [Pubmed] ; 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] ; 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] ; Drew BS, Dixon AF, Dixon JB: Obesity management: update on orlistat. Vasc Health Risk Manag. 2007;3(6):817-21. [Pubmed] ; Wong NN, Cheng-Lai A: Orlistat. Heart Dis. 2000 Mar-Apr;2(2):174-81. [Pubmed] ; Hvizdos KM, Markham A: Orlistat: a review of its use in the management of obesity. Drugs. 1999 Oct;58(4):743-60. [Pubmed] ; Lucas KH, Kaplan-Machlis B: Orlistat--a novel weight loss therapy. Ann Pharmacother. 2001 Mar;35(3):314-28. [Pubmed] ; Curran MP, Scott LJ: Orlistat: a review of its use in the management of patients with obesity. Drugs. 2004;64(24):2845-64. [Pubmed] ; 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]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Selleck Chemicals - S1629

Research Area: Metabolic disease
Biological Activity:
Orlistat is a drug that promotes loss of weight by preventing the digestion and absorption of fat in food. It is intended for use in conjunction with a physician-supervised reduced-calorie diet. Orlistat is the saturated derivative of lipstatin, a potent natural inhibitor of pancreatic lipases isolated from the bacterium Streptomyces toxytricini. However, due to simplicity and stability, orlistat rather than lipstatin was developed into an anti-obesity drug. [1] In vitro experiments demonstrate that orlistat has an IC50 of 122 ng/ml for PL from human duodenal juice, but an IC50 of about 300 ng/ml for LPL. [2]

Sigma Aldrich - O4139

Biochem/physiol Actions
Orlistat, used in obesity research, is a pancreatic lipase inhibitor that acts locally in the gastrointestinal tract to inhibit lipase.
Other Notes
Solution is not completely clear, small particles may remain floating.

Toronto Research Chemicals - O686500

Orlistat is an antiobesity agent. Orlistat is an pancreatic lipase inhibitor.

REFERENCES

• Wong NN, Cheng-Lai A: Orlistat. Heart Dis. 2000 Mar-Apr;2(2):174-81. Pubmed
• 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
• Mancini MC, Halpern A: Pharmacological treatment of obesity. Arq Bras Endocrinol Metabol. 2006 Apr;50(2):377-89. Epub 2006 May 23. Pubmed
• 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
• 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
• Drew BS, Dixon AF, Dixon JB: Obesity management: update on orlistat. Vasc Health Risk Manag. 2007;3(6):817-21. Pubmed
• Hvizdos KM, Markham A: Orlistat: a review of its use in the management of obesity. Drugs. 1999 Oct;58(4):743-60. Pubmed
• Lucas KH, Kaplan-Machlis B: Orlistat--a novel weight loss therapy. Ann Pharmacother. 2001 Mar;35(3):314-28. Pubmed
• Curran MP, Scott LJ: Orlistat: a review of its use in the management of patients with obesity. Drugs. 2004;64(24):2845-64. Pubmed
• 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
• http://en.wikipedia.org/wiki/Orlistat
• Borgstrom, B., et al.: Biochim. Biophys. Acta, 962, 308 (1988)
• Hauptman, J.B., et al.: Am. J. Clin. Nutr., 55, 309S (1988)
• McNeely, W., et al.: Drugs, 56, 241 (1988)
• Hauptman, J. B., et al.: Arch. Fam. Med., 9, 160 (1988)