Accéder au contenu
Merck
Toutes les photos(1)

Key Documents

5.31091

Sigma-Aldrich

Porcn Inhibitor IV, LGK974

Synonyme(s) :

Porcn Inhibitor IV, LGK974, 2-(2ʹ,3-Dimethyl-2,4ʹ-bipyridin-5-yl)-N-(5-(pyrazin-2-yl)pyridin-2-yl)acetamide, Wnt Pathway Inhibitor XXIII, LGK-974

Se connecterpour consulter vos tarifs contractuels et ceux de votre entreprise/organisme


About This Item

Formule empirique (notation de Hill):
C23H20N6O
Numéro CAS:
Poids moléculaire :
396.44
Code UNSPSC :
12352200
Nomenclature NACRES :
NA.77

Pureté

≥97% (HPLC)

Niveau de qualité

Forme

powder

Fabricant/nom de marque

Calbiochem®

Conditions de stockage

OK to freeze
protect from light

Couleur

tan

Solubilité

DMSO: 50 mg/mL

Température de stockage

2-8°C

InChI

1S/C23H20N6O/c1-15-9-17(12-28-23(15)18-5-6-25-16(2)10-18)11-22(30)29-21-4-3-19(13-27-21)20-14-24-7-8-26-20/h3-10,12-14H,11H2,1-2H3,(H,27,29,30)

Clé InChI

XXYGTCZJJLTAGH-UHFFFAOYSA-N

Description générale

A cell-permeable C59 (Cat. No. 500496) structural analog that potently inhibits TM3 cellular Wnt pathway activation-dependent transcription by blocking Wnt secretion from co-cultured L-cells (IC50 from 50 pM to 1.1 nM using Wnt1/2/3/3a/6/7a/9a L-cell transfectants) via direct porcupine (Porcn), but not Wntless, affinity interaction. Shown to inhibit Wnt-dependent proliferation of head and neck squamous cell carcinoma (HNSCC) line HN30 (IC50 = 0.3 nM in 48 h colony formation assay), but not the growth of 293T even at concentrations as high as 20 µM. In mice & rats receiving therapeutic LGK974 oral dosages (up to 5 mg/10 mL/kg/d), a delayed tissue Wnt signaling suppression (max inhibition 7 to 10 h post dosing) is seen due to pre-existing Wnt in tissue, followed by a full recovery of tissue Wnt signalling at 24 h upon drug clearance. The periodic daily inhibition/recovering cycle is shown to result in tumor regression in mice & rats harboring tumors derived from human HNSCC HN30 or tumor fragments from murine mammary tumor virus (MMTV)-Wnt1 transgenic mice, while allowing Wnt signaling-dependent normal tissue homeostasis. Overdosing is reported to result in loss of intestinal epithelium in rats receiving 14 consecutive 20 mg/kg daily oral dosages.
A cell-permeable C59 (Cat. No. 500496) structural analog that potently inhibits Wnt secretion from L-cell Wnt1/2/3/3a/6/7a/9a transfectants (IC50 from 50 pM to 1.1 nM) via direct porcupine (Porcn), but not Wntless, affinity interaction. Shown to inhibit the proliferation of head and neck squamous cell carcinoma (HNSCC) line HN30 (IC50 = 0.3 nM), but not 293T even at a high concentration of 20 µM. In mice & rats receiving therapeutic LGK974 oral dosages (up to 5 mg/10 mL/kg/d), a delayed tissue Wnt signaling suppression (max inhibition 7 to 10 h post dosing) is seen due to pre-existing Wnt in tissue, followed by a full recovery of tissue Wnt signalling at 24 h upon drug clearance. The periodic daily inhibition/recovering cycle is shown to result in tumor regression in mice & rats, while allowing Wnt signaling-dependent normal tissue homeostasis. Overdosing is reported to result in loss of intestinal epithelium in rats receiving 14 consecutive 20 mg/kg daily oral dosages.

Actions biochimiques/physiologiques

Cell permeable: yes
Primary Target
Porcupine
Reversible: yes

Conditionnement

Packaged under inert gas

Avertissement

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Autres remarques

Liu, J., et al. 2013. Proc. Natl. Acad. Sci. USA110, 20224.

Informations légales

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Code de la classe de stockage

11 - Combustible Solids

Classe de danger pour l'eau (WGK)

WGK 3

Point d'éclair (°F)

Not applicable

Point d'éclair (°C)

Not applicable


Certificats d'analyse (COA)

Recherchez un Certificats d'analyse (COA) en saisissant le numéro de lot du produit. Les numéros de lot figurent sur l'étiquette du produit après les mots "Lot" ou "Batch".

Déjà en possession de ce produit ?

Retrouvez la documentation relative aux produits que vous avez récemment achetés dans la Bibliothèque de documents.

Consulter la Bibliothèque de documents

Notre équipe de scientifiques dispose d'une expérience dans tous les secteurs de la recherche, notamment en sciences de la vie, science des matériaux, synthèse chimique, chromatographie, analyse et dans de nombreux autres domaines..

Contacter notre Service technique