Name: LGK974 (WNT974)
Brand: Selleck Chemicals
SKU: S7143
Rating: 5 (92 reviews)

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Batch: Zuiverheid: 99.98%

99.98

Producten Vaak Samen Gebruikt Met LGK974 (WNT974)

Pictilisib (GDC-0941)

When combined with GDC-0941, it exhibits a synergistic effect in MDA-MB-231 cells.

AZD8055

Combination use of this compound and AZD-8055 reduces tumorigenesis and the immunosuppressive effects of early-stage myeloid-derived suppressor cells (eMDSCs) in mice.

Gerelateerde doelwitten	JAK TGF-beta/Smad Wnt/beta-catenin ERK GSK-3 ROCK Hedgehog/Smoothened PKA Secretase STAT
Overige PORCN Inhibitoren	Wnt-C59 (C59) IWP-L6 IWP-O1 ETC-159 GNF-6231

Celkweek, behandeling & werkconcentratie

Cellijnen	Assaytype	Concentratie	Incubatietijd	Formulering	Activiteitsbeschrijving	PMID
HPAF-II	Growth Inhibition Assay	1 μM		DMSO	inhibits the growth of pancreatic cancer cell lines with RNF43mutation	23847203
PaTu 8988S	Growth Inhibition Assay	1 μM		DMSO	inhibits the growth of pancreatic cancer cell lines with RNF43mutation	23847203
Capan-2	Growth Inhibition Assay	1 μM		DMSO	inhibits the growth of pancreatic cancer cell lines with RNF43 mutation	23847203
HPAF-II	Growth Inhibition Assay	1 μM		DMSO	inhibits the growth of pancreatic cancer cell lines with RNF43 mutation	23847203
PaTu8988S	Growth Inhibition Assay	1 μM		DMSO	inhibits the growth of pancreatic cancer cell lines with RNF43 mutation	23847203
293T	Function Assay				IC50 of 0.4 nM to inhibits Wnt signaling in the aforementioned Wnt coculture assay	24277854
293T	Function Assay				IC50 of 1 nM to compete off [3H]-GNF-1331 in a dose-dependent manner	24277854
HT1080	Function assay				Inhibition of porcupine activity (unknown origin) expressed in human HT1080 cells assessed as suppression of Wnt3A-mediated super top flash activity by STF luciferase assay, IC50 = 0.0004 μM.	26522946
L Wnt3A, HEK293	Function assay		48 hrs		Inhibition of Wnt signaling (unknown origin) expressed in mouse L Wnt3A cells co-cultured with HEK293 cells after 48 hrs by Super-top flash reporter gene assay, IC50 = 0.0009 μM.	26647303
L Wnt3A, HEK293	Function assay		48 hrs		Inhibition of porcupine in mouse L Wnt3A cells co-cultured with HEK293 cells after 48 hrs by Super-top flash reporter gene assay, IC50 = 0.0009 μM.	27692509
L Wnt3A, HEK293	Function assay		48 hrs		Inhibition of porcupine in mouse L Wnt3A cells co-cultured with HEK293 cells assessed as suppression of Wnt signaling after 48 hrs by Super-top flash reporter gene assay, IC50 = 0.0009 μM.	29499483
HEK293T	Function assay	0.1 uM	48 hrs		Inhibition of porcupine (unknown origin) in HEK293T cells transfected with pLibin-WNT3A plasmid assessed as reduction in Wnt3A secretion into cell culture medium at 0.1 uM after 48 hrs by Western blot technique	26647303
HEK293T	Function assay	0.1 uM	48 hrs		Inhibition of porcupine in HEK293T cells transfected with pLibin-WNT3A plasmid assessed as reduction in Wnt3A secretion into cell culture medium at 0.1 uM after 48 hrs by Western blot method	27692509
BT-12	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
NB1643	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
OHS-50	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
SK-N-MC	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
HEK293	Function assay	100 nM	48 hrs		Inhibition of porcupine in HEK293 cells transfected with pLibin-WNT3A plasmid assessed as downregulation of LRP6 phosphorylation at 100 nM after 48 hrs by Western blot analysis	29499483
HEK293T	Function assay	100 nM	48 hrs		Inhibition of porcupine in HEK293T cells transfected with pLibin-WNT3A plasmid assessed as reduction in Wnt3A secretion into cell culture medium at 100 nM after 48 hrs by Western blot method	29499483
PA1	Function assay		24 hrs		Inhibition of porcupine-mediated Wnt/beta-catenin signaling in human PA1 cells assessed as downregulation of Axin2 mRNA expression after 24 hrs by real-time PCR analysis	29499483
HEK293	Function assay	100 nM	48 hrs		Inhibition of porcupine in HEK293 cells transfected with pLibin-WNT3A plasmid assessed as downregulation of disheveled 2 phosphorylation at 100 nM after 48 hrs by Western blot analysis	29499483
Klik om meer experimentele gegevens over de cellijn te bekijken

Chemische informatie, Opslag en Stabiliteit

Moleculair gewicht	396.44	Formule	C₂₃H₂₀N₆O	Opslag (Vanaf de ontvangstdatum)	3 jaar-20°Cpoeder
CAS-nr.	1243244-14-5	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	NVP-LGK974, WNT974			Smiles	CC1=CC(=CN=C1C2=CC(=NC=C2)C)CC(=O)NC3=NC=C(C=C3)C4=NC=CN=C4

Oplosbaarheid

In vitro
Batch:

DMSO : 79 mg/mL (199.27 mM)
(Met vocht verontreinigde DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : Insoluble

Ethanol : 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.
Clear solution	5%DMSO 1 Corn oil Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	1.350mg/ml (3.41mM)	Taking the 1 mL working solution as an example, add 50 μL of 27 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
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

Kenmerken	Orally bioavailable Porcupine-specific inhibitor that has been tested in Phase I clinical trials for treatment of malignancies dependent on Wnt ligands.
Targets/IC₅₀/Ki	Porcn (TM3 cells)
In vitro	In de PORCN radioligand bindingsanalyse verplaatst LGK974 (WNT974) effectief [³H]-GNF-1331 met een IC50 van 1 nM en vertoont geen significante cytotoxiciteit in cellen tot 20 5M. Het vertoont vergelijkbare remmende activiteiten tegen alle geteste Wnts met IC50 varicrend van 0,05 tot 2,4 nM, wat consistent is met het genetisch verlies van het PORCN-fenotype. Deze verbinding remt specifiek de groei van drie RNF43-mutante cellijnen, HPAF-II, PaTu 8988S en Capan-2.
In vivo	In een murien MMTV-Wnt1 tumormodel en een humaan plaveiselcelcarcinoommodel van hoofd en nek (HN30), remt LGK974 (WNT974) (3 mg/kg) Wnt-signalering in vivo en induceert tumorregressie zonder significant gewichtsverlies bij de muizen. Deze verbinding (5 mg/kg, p.o., BID) remt ook de tumorgroei van RNF43-mutante pancreastumoren (HPAF-II en Capan-2) in vivo.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/24277854/ [2] https://pubmed.ncbi.nlm.nih.gov/23847203/

Toepassingen

Methoden	Biomarkers	Afbeeldingen	PMID
Western blot	Nrf2 / Wnt3A / HO-1 / NQO-1 / Survivin NF-κB / IκB / p-IκB p-LRP6 / Axin / p-GSK3β / p-β-catenin / β-catenin		28627706
Immunofluorescence	α1, 6-fucosylation FUT8 beta-catenin		28798691

Informatie klinische proef

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

NCT-nummer	Rekrutering	Aandoeningen	Sponsor/Medewerkers	Startdatum	Fasen
NCT01351103	Active not recruiting	Pancreatic Cancer\|BRAF Mutant Colorectal Cancer\|Melanoma\|Triple Negative Breast Cancer\|Head and Neck Squamous Cell Cancer\|Cervical Squamous Cell Cancer\|Esophageal Squamous Cell Cancer\|Lung Squamous Cell Cancer	Novartis Pharmaceuticals\|Novartis	December 1 2011	Phase 1

Technische ondersteuning

Gebruiksaanwijzing

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

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Veelgestelde vragen

Vraag 1:
If it is a lipophilic or hydrophilic substance?

Antwoord:
It is a lipophilic compound.

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LGK974 (WNT974) PORCN remmer

Chemische structuur

Moleculair gewicht: 396.44