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

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Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.98%

99.98

Gerelateerde doelwitten	Dehydrogenase HSP Transferase P450 (e.g. CYP17) PDE phosphatase PPAR Vitamin Carbohydrate Metabolism Mitochondrial Metabolism
Overige Lipase Inhibitoren	Tanshinone IIA Atglistatin JZL184 Pristimerin Schaftoside ABX-1431 XEN445 Cetilistat Pancreatin URB602

Celkweek, behandeling & werkconcentratie
(Cell Culture, Treatment & Working Concentration)

Cellijnen	Assaytype	Concentratie	Incubatietijd	Activiteitsbeschrijving	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
Klik om meer experimentele gegevens over de cellijn te bekijken

Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Moleculair gewicht	495.73	Formule	C₂₉H₅₃NO₅	Opslag (Vanaf de ontvangstdatum)	3 jaar-20°Cpoeder
CAS-nr.	96829-58-2	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	Tetrahydrolipstatin,Ro 18-0647			Smiles	CCCCCCCCCCCC(CC1C(C(=O)O1)CCCCCC)OC(=O)C(CC(C)C)NC=O

Oplosbaarheid (Solubility)

In vitro
Batch:

DMSO : 99 mg/mL (199.7 mM)
(Met vocht verontreinigde DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Ethanol : 99 mg/mL

Water : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Moleculair gewicht
=	×	×

Verdunningscalculator Moleculair gewicht calculator

In vivo Batch:
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.

In vivo Formuleringscalculator (Heldere oplossing)

Stap 1: Voer de onderstaande informatie in (Aanbevolen: Een extra dier voor het geval van verlies tijdens het experiment)

Dosering: mg/kg Gemiddeld gewicht van dieren: g Doseervolume per dier:μL Aantal dieren:

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in het gedeelte Oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-mastervloeistof: mg geneesmiddel vooraf opgelost in μL DMSO ( Concentratie mastervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de partij geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toeμL PEG300, mengen en helder maken, voeg vervolgens toeμL Tween 80, mengen en helder maken, voeg vervolgens toe μL ddH₂O, mengen en helder maken.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toe μL Maïsolie, mengen en helder maken.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysische methoden zoals vortexen, echografie of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme (Mechanism of Action)

Targets/IC₅₀/Ki	lipase (Cell-free assay) Fatty acid synthesis (Cell-free assay)
In vitro	Orlistat, een remmer van lipases en Fatty Acid Synthase, wordt oraal gebruikt voor de langetermijnbehandeling van obesitas. Deze verbinding vertoont antiproliferatieve activiteit tegen kankercellen in vitro. Er is vastgesteld dat het pro-apoptotic NOXA protein versterkt.
In vivo	Orlistat, oraal toegediend, wordt minimaal geabsorbeerd door het maag-darmkanaal en is in staat de absorptie van een groot percentage lipiden te voorkomen, waardoor de lipidenvoorziening uit externe bronnen wordt verminderd. Vanwege de extreem lage orale biologische beschikbaarheid zijn de effecten van deze verbinding grotendeels beperkt tot het maag-darmkanaal, waar het pancreaslipase inactiveert. Daarom zouden de formulering en toedieningsroute moeten worden gewijzigd om tumoren van de borst, prostaat, enzovoort te behandelen. Dit chemische middel stopt de proliferatie van tumorcellen, induceert apoptose van tumorcellen en remt de groei van PC-3-tumoren in naakte muizen. Een farmacokinetische analyse van deze verbinding (155 mg/kg) toegediend via i.p. injectie toonde piekniveaus in het bloed van ~10 μM 2 uur na toediening (gegevens niet getoond). Na deze tijd daalden de bloedspiegels van het medicijn snel.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/26035182/ [2] https://pubmed.ncbi.nlm.nih.gov/15026345/

Toepassingen (Applications)

Methoden	Biomarkers	Afbeeldingen	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

Informatie klinische proef (Clinical Trial Information)

(gegevens van https://clinicaltrials.gov, bijgewerkt op 2024-05-22)

NCT-nummer	Rekrutering	Aandoeningen	Sponsor/Medewerkers	Startdatum	Fasen
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

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Orlistat Lipase Remmer

Chemische structuur

Moleculair gewicht: 495.73

Kwaliteitscontrole (Quality Control)

Celkweek, behandeling & werkconcentratie
(Cell Culture, Treatment & Working Concentration)

Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo Formuleringscalculator (Heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Toepassingen (Applications)

Informatie klinische proef (Clinical Trial Information)

Orlistat Lipase Remmer

Chemische structuur

Moleculair gewicht: 495.73

Kwaliteitscontrole (Quality Control)

Celkweek, behandeling & werkconcentratie (Cell Culture, Treatment & Working Concentration)

Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo Formuleringscalculator (Heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Toepassingen (Applications)

Informatie klinische proef (Clinical Trial Information)

Celkweek, behandeling & werkconcentratie
(Cell Culture, Treatment & Working Concentration)