Name: Orlistat
Brand: Selleck Chemicals
SKU: S1629
Rating: 5 (18 reviews)

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Contrôle qualité

Lot : Pureté : 99.98%

99.98

Cibles apparentées	Dehydrogenase HSP Transferase P450 (e.g. CYP17) PDE phosphatase PPAR Vitamin Carbohydrate Metabolism Mitochondrial Metabolism
Autre Lipase Inhibiteurs	Tanshinone IIA Atglistatin JZL184 Pristimerin XEN445 Cetilistat Pancreatin Schaftoside ABX-1431 URB602

Culture cellulaire, traitement et concentration de travail

Lignées cellulaires	Type dessai	Concentration	Temps dincubation	Description de lactivité	PMID
HEK293T	Function assay			Inhibition of human DAGLalpha expressed in HEK293T cell membrane using [14C]SAG substrate in detergent free solution by FRET assay, IC50=0.01 μM	22738638
COS	Function assay		15 mins	Inhibition of human recombinant DAGLalpha expressed in African green monkey COS cells using sn-1-stearoyl-2-[14C]-arachidonoyl-glycerol as substrate incubated for 15 mins by beta counting analysis, IC50 = 0.001 μM.	26917221
COS7	Function assay		20 mins	Inhibition of recombinant human HL expressed in COS7 cells using PED-A1 containing DMPG vesicles as substrate pretreated for 20 mins followed by substrate addition and measured every 20 secs for 10 mins by fluorescence assay, IC50 = 0.003 μM.	30613337
HT1080	Function assay		20 mins	Inhibition of endothelial lipase in human HT1080 cells using PED-A1 containing DMPG vesicles as substrate pretreated for 20 mins followed by substrate addition and measured every 20 secs for 10 mins by fluorescence assay, IC50 = 0.006 μM.	30613337
HEK293F	Function assay		20 mins	Inhibition of recombinant human PL expressed in HEK293F cells using PED-A1 containing DMPG vesicles as substrate pretreated for 20 mins followed by substrate addition and measured every 20 secs for 10 mins by fluorescence assay, IC50 = 0.006 μM.	30613337
HEK293	Function assay	1 uM	10 mins	Inhibition of human ABHD6 expressed in HEK293 cells at 1 uM pre-incubated for 10 mins before 2-AG substrate addition followed by rapid 40 fold compound dilution measured after 10 mins by HPLC method, IC50 = 0.01318 μM.	26344596
HEK293	Function assay	1 uM	10 mins	Inhibition of human ABHD6 expressed in HEK293 cells at 1 uM pre-incubated for 10 mins before 2-AG substrate addition followed by rapid 40 fold compound dilution measured after 30 mins by HPLC method, IC50 = 0.01413 μM.	26344596
HEK293	Function assay	1 uM	10 mins	Inhibition of human ABHD6 expressed in HEK293 cells at 1 uM pre-incubated for 10 mins before 2-AG substrate addition followed by rapid 40 fold compound dilution measured after 60 mins by HPLC method, IC50 = 0.01995 μM.	26344596
N18TG2	Function assay		20 mins	Inhibition of DAGLalpha in mouse N18TG2 cells assessed as inhibition of ionomycin-induced formation of 2-AG incubated for 20 mins by LC-MS analysis, IC50 = 0.02 μM.	26917221
HEK293T	Function assay			Inhibition of recombinant BAT5 transfected in HEK293T cells by SDS-PAGE using rhodamine-tagged FP probe, IC50 = 0.03 μM.	18657971
HEK293	Function assay	1 uM	10 mins	Inhibition of human ABHD6 expressed in HEK293 cells at 1 uM pre-incubated for 10 mins before 2-AG substrate addition followed by rapid 40 fold compound dilution measured after 90 mins by HPLC method, IC50 = 0.03715 μM.	26344596
HEK293	Function assay			Inhibition of human ABHD6 containing pCMV6-AC-hABHD6 transfected into HEK293 cells, IC50 = 0.04786 μM.	25752982
HEK293	Function assay			Inhibition of human ABHD6 containing pCMV6-AC-hABHD6 transfected into HEK293 cells, IC50 = 0.048 μM.	25752982
HEK293T	Function assay			Inhibition of recombinant PLA2g7 transfected in HEK293T cells by SDS-PAGE using rhodamine-tagged FP probe, IC50 = 0.05 μM.	18657971
COS7	Function assay			Inhibition of human recombinant DAGLalpha overexpressed in african green monkey COS7 cells, IC50 = 0.06 μM.	18657971
COS7	Function assay			Inhibition of human recombinant DAGLbeta overexpressed in african green monkey COS7 cells, IC50 = 0.06 μM.	18657971
COS7	Function assay		20 mins	Inhibition of recombinant human LPL expressed in COS7 cells using PED-A1 containing DMPG vesicles as substrate pretreated for 20 mins followed by substrate addition and measured every 20 secs for 10 mins by fluorescence assay, IC50 = 0.066 μM.	30613337
HEK293T	Function assay			Inhibition of recombinant ABHD12 transfected in HEK293T cells by SDS-PAGE using rhodamine-tagged FP probe, IC50 = 0.08 μM.	18657971
HEK293	Function assay			Inhibition of human ABHD12 containing pCMV6-XL4-hABHD12 transfected into HEK293 cells, IC50 = 0.19 μM.	25752982
HEK293	Function assay		10 mins	Inhibition of human ABHD12 expressed in HEK293 cells pre-incubated for 10 mins before 2-AG substrate addition by HPLC method, IC50 = 0.19 μM.	26344596
HEK293	Function assay			Inhibition of human ABHD12 containing pCMV6-XL4-hABHD12 transfected into HEK293 cells, IC50 = 0.19055 μM.	25752982
HEK293	Function assay		10 mins	Inhibition of human ABHD12 expressed in HEK293 cells pre-incubated for 10 mins before 2-AG substrate addition by HPLC method, IC50 = 0.19055 μM.	26344596
HEK293	Function assay			Displacement of [3H]CP-55940 from human recombinant CB1 receptor expressed in HEK293 cells by scintillation counting, Ki = 2.5 μM.	18831576
BxPC3	Function assay		10 to 14 days	Inhibition of survival of human BxPC3 cells after 10 to 14 days by crystal violet staining-based colony formation assay, IC50 = 8.45 μM.	25513712
MDA-MB-231	Cytotoxicity assay			Cytotoxicity against human MDA-MB-231 cells assessed as reduction in cell viability, IC50 = 13 μM.	29541373
MDA-MB-435	Cytotoxicity assay		48 hrs	Cytotoxicity against human MDA-MB-435 cells after 48 hrs by Cell titer assay, IC50 = 16.8 μM.	18710210
HepG2 (DPX-2)	Function assay		24 hrs	Activation of human PXR expressed in human HepG2 (DPX-2) cells assessed as induction of CYP3A4 after 24 hrs by luminescent analysis, EC50 = 28.2 μM.	20966043
COS7	Function assay			Inhibition of recombinant DAGLbeta overexpressed in african green monkey COS7 cells assessed as accumulation of 2-arachidonoylglycerol by Western blotting	18657971
COS7	Function assay			Inhibition of recombinant DAGLalpha overexpressed in african green monkey COS7 cells assessed as accumulation of 2-arachidonoylglycerol by Western blotting	18657971
MDA-MB-435	Apoptosis assay	25 uM	72 hrs	Induction of apoptosis in human MDA-MB-435 cells assessed as DNA fragmentation at 25 uM after 72 hrs	18710210
HEK293	Function assay	1 uM	10 mins	Reversible inhibition of human ABHD6 expressed in HEK293 cells at 1 uM pre-incubated for 10 mins before 2-AG substrate addition followed by rapid 40 fold compound dilution measured after 10 to 90 mins by HPLC method	26344596
LNCAP	Function assay	20 uM	48 hrs	Induction of cholesterol metabolism deregulation in human LNCAP cells assessed as reduction in NBD-cholesterol uptake at 20 uM after 48 hrs by DAPI/Alexa fluor 633 phalloidin staining based high-content imaging analysis	29474071
BV2	Function assay		30 mins	Inhibition of ABHD6 in mouse BV2 cells preincubated for 30 mins and subsequent addition of [3H]-2-OG substrate measured after 15 mins by liquid scintillation counting method	28284861
BV2	Function assay		30 mins	Inhibition of ABHD12 in mouse BV2 cells preincubated for 30 mins and subsequent addition of [3H]-2-OG substrate measured after 15 mins by liquid scintillation counting method	28284861
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Informations chimiques, stockage et stabilité

Poids moléculaire	495.73	Formule	C₂₉H₅₃NO₅	Stockage (À partir de la date de réception)	3 ans-20°Cpoudre
N° CAS	96829-58-2	Télécharger le SDF		Stockage des solutions mères	1 an-80°Cen solvant 1 mois-20°Cen solvant
Synonymes	Tetrahydrolipstatin,Ro 18-0647			Smiles	CCCCCCCCCCCC(CC1C(C(=O)O1)CCCCCC)OC(=O)C(CC(C)C)NC=O

Solubilité

In vitro
Lot:

DMSO : 99 mg/mL (199.7 mM)
(Le DMSO contaminé par lhumidité peut réduire la solubilité. Utiliser du DMSO frais et anhydre.)

Ethanol : 99 mg/mL

Water : Insoluble

Calculateur de molarité

Masse	Concentration	Volume	Poids moléculaire
=	×	×

Calculateur de dilution Calculateur de poids moléculaire

In vivo Lot:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

Calculateur de formulation in vivo (Solution claire)

Étape 1 : Entrez les informations ci-dessous (Recommandé : Un animal supplémentaire pour tenir compte des pertes pendant lexpérience)

Dosage : mg/kg Poids moyen des animaux : g Volume de dosage par animal :μL Nombre danimaux :

Étape 2 : Entrez la formulation in vivo (Ceci nest que le calculateur, pas la formulation. Veuillez nous contacter dabord sil ny a pas de formulation in vivo dans la section Solubilité.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Résultats du calcul :

Concentration de travail : mg/ml;

Méthode de préparation du liquide maître DMSO : mg médicament prédissous dans μL DMSO ( Concentration du liquide maître mg/mL, Veuillez nous contacter dabord si la concentration dépasse la solubilité du DMSO du lot de médicament. )

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, ajouter ensuiteμL PEG300, mélanger et clarifier, ajouter ensuiteμL Tween 80, mélanger et clarifier, ajouter ensuite μL ddH₂O, mélanger et clarifier.

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, ajouter ensuite μL Huile de maïs, mélanger et clarifier.

Remarque : 1. Assurez-vous que le liquide est clair avant dajouter le solvant suivant.
2. Assurez-vous dajouter le(s) solvant(s) dans lordre. Vous devez vous assurer que la solution obtenue lors de lajout précédent est une solution claire avant de procéder à lajout du solvant suivant. Des méthodes physiques telles que le vortex, les ultrasons ou le bain-marie peuvent être utilisées pour faciliter la dissolution.

Mécanisme daction

Targets/IC₅₀/Ki	lipase (Cell-free assay) Fatty acid synthesis (Cell-free assay)
In vitro	L'Orlistat, un inhibiteur des lipases et de Fatty Acid Synthase, est utilisé par voie orale pour le traitement à long terme de l'obésité. Ce composé montre une activité antiproliférative contre les cellules cancéreuses in vitro. Il a été constaté qu'il augmente la protéine pro-apoptotic NOXA.
In vivo	L'Orlistat, administré par voie orale, est peu absorbé par le tractus gastro-intestinal et est capable de prévenir l'absorption d'un grand pourcentage de lipides, réduisant ainsi l'apport lipidique provenant de sources externes. En raison de sa très faible biodisponibilité orale, les effets de ce composé sont largement confinés au tractus gastro-intestinal, où il inactive la lipase pancréatique. Par conséquent, la formulation et la voie d'administration devraient être modifiées pour traiter les tumeurs du sein, de la prostate, etc. Cette substance chimique arrête la prolifération des cellules tumorales, induit l'apoptose des cellules tumorales et inhibe la croissance des tumeurs PC-3 chez les souris nues. Une analyse pharmacocinétique de ce composé (155 mg/kg) administré par injection i.p. a montré que les niveaux sanguins maximaux étaient d'environ 10 μM 2 h après l'administration (données non présentées). Au-delà de ce temps, les niveaux sanguins du médicament ont diminué rapidement.
Références	[1] https://pubmed.ncbi.nlm.nih.gov/26035182/ [2] https://pubmed.ncbi.nlm.nih.gov/15026345/

Applications

Méthodes	Biomarqueurs	Images	PMID
Western blot	FASN / AR / p-AKT / p-p53 / p53 / VEGF / Cyclin D1 / Bcl-2 / Cleaved caspase-3		31527721
Growth inhibition assay	Cell viability		28387458

Informations sur lessai clinique

(données de https://clinicaltrials.gov, mis à jour le 2024-05-22)

Numéro NCT	Recrutement	Conditions	Sponsor/Collaborateurs	Date de début	Phases
NCT01755676	Completed	Obesity	EMS	September 2016	Phase 3
NCT02141230	Withdrawn	Weight Loss	GlaxoSmithKline\|Hamell	December 2015	Not Applicable
NCT01719419	Withdrawn	Overweight	Pennington Biomedical Research Center	March 2012	Not Applicable
NCT01332448	Completed	Obesity	GlaxoSmithKline	February 2010	--
NCT01414465	Completed	Overweight	University of Campinas Brazil\|Germed Pharma	October 2009	Not Applicable

Support technique

Instructions de manipulation

Tel: +1-832-582-8158 Ext:3

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Orlistat Lipase inhibiteur

Structure chimique

Poids moléculaire: 495.73