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Orlistat Lipase Inibitore

N. Cat.: S1629

Orlistat è un inibitore generale della lipase con IC50 di 122 ng/ml per PL dal succo duodenale umano. Il trattamento con questo composto riduce la proliferazione, induce l'apoptosis e arresta il ciclo cellulare.
Orlistat Lipase Inibitore Chemical Structure

Struttura chimica

Peso molecolare: 495.73

Vai a

Controllo Qualità (Quality Control)

Lotto: Purezza: 99.98%
99.98

Coltura cellulare, trattamento e concentrazione di lavoro
(Cell Culture, Treatment & Working Concentration)

Linee cellulari Tipo di saggio Concentrazione Tempo di incubazione Formulazione Descrizione dell'attività 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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Informazioni chimiche, conservazione e stabilità (Chemical Information, Storage & Stability)

Peso molecolare 495.73 Formula

C29H53NO5

 Conservazione (Dalla data di ricezione)
N. CAS 96829-58-2 Scarica SDF Conservazione delle soluzioni stock

Sinonimi Tetrahydrolipstatin,Ro 18-0647 Smiles CCCCCCCCCCCC(CC1C(C(=O)O1)CCCCCC)OC(=O)C(CC(C)C)NC=O

Solubilità (Solubility)

In vitro
Lotto:

DMSO : 99 mg/mL (199.7 mM)
(Il DMSO contaminato da umidità può ridurre la solubilità. Utilizzare DMSO fresco e anidro.)

Ethanol : 99 mg/mL

Water : Insoluble

Calcolatore di Molarità

Massa Concentrazione Volume Peso molecolare
Calcolatore di Diluizione Calcolatore del Peso Molecolare

In vivo
Lotto:

Calcolatore di formulazione in vivo (Soluzione chiara)

Passo 1: Inserire le informazioni di seguito (Consigliato: Un animale aggiuntivo per tenere conto della perdita durante l'esperimento)

mg/kg g μL

Passo 2: Inserire la formulazione in vivo (Questo è solo il calcolatore, non la formulazione. Contattateci prima se non c'è una formulazione in vivo nella sezione Solubilità.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Risultati del calcolo:

Concentrazione di lavoro: mg/ml;

Metodo per preparare il liquido master di DMSO: mg farmaco predissolto in μL DMSO ( Concentrazione del liquido master mg/mL, Vi preghiamo di contattarci prima se la concentrazione supera la solubilità del DMSO del lotto del farmaco. )

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungereμL PEG300, mescolare e chiarire, quindi aggiungereμL Tween 80, mescolare e chiarire, quindi aggiungere μL ddH2O, mescolare e chiarire.

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungere μL Olio di mais, mescolare e chiarire.

Nota: 1. Si prega di assicurarsi che il liquido sia limpido prima di aggiungere il solvente successivo.
2. Assicurarsi di aggiungere il/i solvente/i in ordine. È necessario assicurarsi che la soluzione ottenuta, nell'aggiunta precedente, sia una soluzione limpida prima di procedere all'aggiunta del solvente successivo. Metodi fisici come il vortex, gli ultrasuoni o il bagno d'acqua calda possono essere utilizzati per facilitare la dissoluzione.

Meccanismo d'azione (Mechanism of Action)

Targets/IC50/Ki
lipase
(Cell-free assay)
Fatty acid synthesis
(Cell-free assay)
In vitro
Orlistat, an inhibitor of lipases and fatty acid synthase, is used orally for long-term treatment of obesity. This compound shows antiproliferative activity against cancer cells in vitro. It has been found to augment pro-apoptotic NOXA protein.
In vivo
Orlistat, administered by oral route, is minimally absorbed by the gastrointestinal tract and is able to prevent the absorption of a large percentage of lipids, thereby reducing lipid supply from outside sources. Because of its extremely low oral bioavailability, the effects of this compound are largely confined to the gastrointestinal tract, where it inactivates pancreatic lipase. Therefore, the formulation and route of delivery would have to be changed to treat tumors of the breast, prostate, and so on. This chemical halts tumor cell proliferation, induces tumor cell apoptosis, and inhibits the growth of PC-3 tumors in nude mice. A pharmacokinetic analysis of this compound (155 mg/kg) administered by i.p. injection showed peak blood levels to be ∼10 μM 2 h after dosing (data not shown). Beyond this time, blood levels of the drug decayed rapidly.
Riferimenti

Applicazioni (Applications)

Metodi Biomarcatori Immagini PMID
Western blot FASN / AR / p-AKT / p-p53 / p53 / VEGF / Cyclin D1 / Bcl-2 / Cleaved caspase-3
S1629-WB1
31527721
Growth inhibition assay Cell viability
S1629-viability1
28387458

Informazioni sullo studio clinico (Clinical Trial Information)

(dati da https://clinicaltrials.gov, aggiornato il 2024-05-22)

Numero NCT Reclutamento Condizioni Sponsor/Collaboratori Data di inizio Fasi
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