Orlistat

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Warnung

• Gefahrenhinweise

  H302：Gesundheitsschädlich bei Verschlucken.

  H412：Schädlich für Wasserorganismen, mit langfristiger Wirkung.

• Sicherheit

  P273：Freisetzung in die Umwelt vermeiden.

Orlistat Chemische Eigenschaften,Einsatz,Produktion Methoden

• Beschreibung

  Orlistat was launched in the UK as Xenical for the long-term treatment of obesity, preferably in conjunction with a moderately reduced calorie diet. Orlistat is a tetrahydro-derivative of the natural hypolipaemic lipstatin (from Streptomyces toxyfncini) and can be obtained either by hydrogenation of lipstatine or by several different synthetic ways involving many steps from ( S ) - rnalic acid. Orlistat is a potent inhibitor of gastrointestinal lipases required for the lipolysis and digestion of dietary fat, in particular of pancreatic lipase ; as a result, it prevents the absorption of about one third of the fat contained in food and acts as an effective weight-reducing therapy. The outcomes of several clinical trials involving thousands of obese patients showed that Orlistat promotes a significant weight loss (often between 5 and 10% after one year) and improves cardiovascular risk factors such as total cholesterol, LDL/HDL ratio, blood glucose levels, insulin, blood pressure. Orlistat has minimal systemic absorption, the majority of the compound itself being recovered in the feces ; it does not affect other gastrointestinal processes, or the absorption of other rnacronutrients such as carbohydrates and proteins.

• Beschreibung

  Orlistat is a digestive lipase inhibitor. It inhibits diacylglycerol lipase α (DAGLα), DAGLβ, α/β-hydrolase domain-containing protein 12 (ABHD12), ABHD16A, and platelet-activating factor acetylhydrolase (PAF-AH; IC₅₀s = 0.06, 0.1, 0.08, 0.03, and 0.05 μM, respectively), as well as pancreatic lipase and hormone-sensitive lipase (IC₅₀s = 0.65 and 2.1 μg/ml, respectively) but does not inhibit fatty acid amide hydrolase (FAAH) or KIAA1363 (IC₅₀s = >100 μM for both). Orlistat decreases ionomycin-induced production of the endocannabinoid 2-arachidonoyl glycerol (2-AG) in N18TG2 murine neuroblastoma cells when used at a concentration of 1 μM. It also inhibits fatty acid synthase (FASN; K_iapp = ~0.1 μM for the human enzyme) and the proliferation of PC3 prostate cancer cells in a concentration-dependent manner. Orlistat (10 mg/kg) decreases serum cholesterol levels and total body weight in a mouse model of obesity induced by a high-fat diet. Formulations containing orlistat have been used in the treatment of adult obesity.

• Chemische Eigenschaften

  Off-White Solid

• Originator

  Roche (Switzerland)

• Verwenden

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

• Verwenden

  antidiabetic

• Verwenden

  An antiobesity agent. A pancreatic lipase inhibitor. Antiobesity agent.

• Verwenden

  Tetrahydrolipstatin (orlistat) is a semi-synthetic derivative of lipstatin, a metabolite isolated from Streptomyces toxytricini. Tetrahydrolipstatin acts as a potent, irreversible inhibitor of pancreatic lipase. In vivo, it blocks the absorption of triglycerides while allowing fatty acid absorption. Tetrahydrolipstatin is widely used for the treatment of obesity.

• Definition

  ChEBI: Orlistat is a carboxylic ester resulting from the formal condensation of the carboxy group of N-formyl-L-leucine with the hydroxy group of (3S,4S)-3-hexyl-4-[(2S)-2-hydroxytridecyl]oxetan-2-one. A pancreatic lipase inhibitor, it is used as an anti-obesity drug. It has a role as an EC 3.1.1.3 (triacylglycerol lipase) inhibitor, a bacterial metabolite, an EC 2.3.1.85 (fatty acid synthase) inhibitor and an anti-obesity agent. It is a beta-lactone, a L-leucine derivative, a member of formamides and a carboxylic ester.

• Trademarks

  Xenical (Roche).

• Synthesis Reference(s)

  [1]Jagtap, U. A., & Paul, A. T. (2025). Synthetic pancreatic lipase inhibitors in obesity treatment: current updates on <i>in silico</i> design, synthesis, bioactivity, and SAR. RSC Medicinal Chemistry, 16(12), 5787–5842. https://doi.org/10.1039/d5md00373c
  [2]Tang, Y., Zhou, Y., Zhao, Q., Zhao, Q., & Wang, Z. (2020). Enzymatic synthesis of an orlistat intermediate using a mutant short-chain dehydrogenase from Novosphingobium aromaticivorans. Process Biochemistry, 95, 235–241. https://doi.org/10.1016/j.procbio.2020.02.015
  [3]Ma, G., Zancanella, M., Oyola, Y., Richardson, R. D., Smith, J. W., & Romo, D. (2006). Total Synthesis and Comparative Analysis of Orlistat, Valilactone, and a Transposed Orlistat Derivative:  Inhibitors of Fatty Acid Synthase. Organic Letters, 8(20), 4497–4500. https://doi.org/10.1021/ol061651o

• Allgemeine Beschreibung

  Pharmaceutical secondary standards for application in quality control, provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards.
  Orlistat is a specific lipase inhibitor derived from lipostatin, which is naturally produced by Streptomyces toxytricini. Lipase inhibition induced by orlistat reduces the absorption of dietary fat, thereby contributing to caloric deficit.

• Biologische Aktivität

  Hypolipemic pancreatic, gastric and carboxylester lipase inhibitor. Exhibits no activity at phospholipase A 2 , liver esterase, trypsin and chymotrypsin. Inhibits the thioesterase domain of fatty acid synthase, leading to cell cycle arrest at the G 1 /S boundary in vitro . Prevents the absorption of approximately one third of fat from food and exhibits progastrokinetic, antiobesity and antihypercholesterolemic activity in vivo .

• Biochem/physiol Actions

  Orlistat, used in obesity research, is a pancreatic lipase inhibitor that acts locally in the gastrointestinal tract to inhibit lipase.

• Clinical Use

  Adjunct in obesity

• Synthese

  Orlistat can be prepared from the natural compound lipstatin or by fully chemical synthetic routes; one route employs lactonization with ZnCl2, (R)-3-(((l2-boraneyl-t)thio)oxy)pentanal (7), and thiopyridyl ketene acetals (8) as starting materials, followed by a Mitsunobu reaction with N-formyl leucine (10) to afford (−)-tetrahydrolipstatin, while first- and second-generation enantioselective syntheses deliver the product during the Mitsunobu coupling and demonstrate the key intermediate 21 on a large scale[1][2]. A formal synthesis of orlistat proceeds through hydrogenation of intermediate 9a under standard conditions to afford hydroxy-β-lactone 6 in nearly quantitative yield[3]. A formal synthesis of orlistat is achieved via cross metathesis with excess n-nonene in the presence of the first-generation Grubbs catalyst[3].
  

• Arzneimittelwechselwirkung

  Potentially hazardous interactions with other drugs
  Acarbose: avoid concomitant administration.
  Amiodarone: possibly slightly reduces absorption.1
  Anticoagulants: monitor INR more frequently (due to reduction in vitamin K absorption).1
  Antiepileptics: possible increased risk of convulsions.
  Antivirals: absorption of abacavir, atazanavir, darunavir, didanosine, efavirenz, elvitegravir, emtricitabine, enfuvirtide, etravirine, fosamprenavir, indinavir, lamivudine, lopinavir, maraviroc, nevirapine, raltegravir, rilpivirine, ritonavir, saquinavir, stavudine, tenofovir, tipranavir and zidovudine possibly reduced.
  Ciclosporin: possibly reduces absorption of ciclosporin.
  Tacrolimus: possibly reduces absorption of tacrolimus.1
  Thyroid hormones: possible increased risk of hypothyroidism with levothyroxine.
  Vitamins: may reduce the absorption of fat soluble vitamins.

• Stoffwechsel

  Orlistat is minimally absorbed and has no defined systemic pharmacokinetics. The metabolism of orlistat occurs mainly within the gastrointestinal wall to form 2 major inactive metabolites, M1 (4-member lactone ring hydrolysed) and M3 (M1 with N-formyl leucine moiety cleaved).
  Faecal excretion of the unabsorbed drug is the major route of elimination. Approximately 97% of the administered dose is excreted in faeces and 83% of that as unchanged orlistat.

• Lager

  +4°C

• Einzelnachweise

  [1] TIZIANA BISOGNO . Development of the first potent and specific inhibitors of endocannabinoid biosynthesis[J]. Biochimica et biophysica acta. Molecular and cell biology of lipids, 2006, 1761 2: Pages 205-212. DOI:10.1016/j.bbalip.2005.12.009
  [2] P HADVÁRY. The lipase inhibitor tetrahydrolipstatin binds covalently to the putative active site serine of pancreatic lipase.[J]. The Journal of Biological Chemistry, 1991, 266 4: 2021-2027.
  [3] STEVEN J KRIDEL. Orlistat is a novel inhibitor of fatty acid synthase with antitumor activity.[J]. Cancer research, 2004, 64 6: 2070-2075. DOI:10.1158/0008-5472.can-03-3645
  [4] ANNE BALLINGER  Steven R P. Orlistat: its current status as an anti-obesity drug[J]. European journal of pharmacology, 2002, 440 2: Pages 109-117. DOI:10.1016/s0014-2999(02)01422-x

Orlistat Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

Global(822)Suppliers

96829-58-2, Orlistat Verwandte Suche: