Orlistat

Bezeichnung:Orlistat

CAS-Nr96829-58-2

Englisch Name:Orlistat

CBNumberCB2431985

SummenformelC29H53NO5

Molgewicht495.73

MOL-Datei96829-58-2.mol

Orlistat physikalisch-chemischer Eigenschaften

Schmelzpunkt	<50 °C
Siedepunkt	615.9±30.0 °C(Predicted)
alpha	D20 -32.0° (c = 1 in chloroform)
Dichte	0.976±0.06 g/cm3(Predicted)
storage temp.	2-8°C
Löslichkeit	DMSO: 19 mg/mL
Aggregatzustand	solid
pka	14.59±0.23(Predicted)
Farbe	white
Biologische Quelle	synthetic (organic)
Merck	14,6869
Stabilität	Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 1 week.
InChIKey	AHLBNYSZXLDEJQ-FWEHEUNISA-N
SMILES	C(O[C@H](C[C@H]1[C@H](CCCCCC)C(=O)O1)CCCCCCCCCCC)(=O)[C@H](CC(C)C)NC=O
CAS Datenbank	96829-58-2(CAS DataBase Reference)

Sicherheit

WGK Germany	3
RTECS-Nr.	OH3167600
HS Code	29322090
Giftige Stoffe Daten	96829-58-2(Hazardous Substances Data)

Gefahreninformationscode (GHS)

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).
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
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) Bisogno et al. (2006), Development of the first potent and specific inhibitors of endocannabinoid biosynthesis; Biochim. Biophys. Acta, 1761 205 2) Hadvary et al. (1991), The lipase inhibitor tetrahydrolipstatin bind covalently to the putative active site serine of pancreatic lipase; J. Biol. Chem., 266 2021 3) Kridel et al. (2004), Orlistat is a novel inhibitor of fatty acid synthase with antitumor activity; Cancer Res., 64 2070 4) Ballinger and Peikin (2002), Orlistat: it’s current status as an anti-obesity drug; Eur. J. Pharmacol., 440 109

Orlistat Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

96829-58-2, Orlistat Verwandte Suche:

Send Inquriy