Catalog No.S8392

NCB-0846 Chemical Structure

Molecular Weight(MW): 375.42

NCB-0846 is a novel, orally small-molecule Wnt inhibitor that inhibits TNIK (TRAF2 and NCK-Interacting Kinase) with an IC50 value of 21 nM.

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Description NCB-0846 is a novel, orally small-molecule Wnt inhibitor that inhibits TNIK (TRAF2 and NCK-Interacting Kinase) with an IC50 value of 21 nM.
TNIK [1]
(Cell-free assay)
21 nM
In vitro

NCB-0846 blocks Wnt signalling and shows marked anti-tumour and anti-CSC activities. NCB-0846 binds to TNIK in an inactive conformation, and this binding mode seems to be essential for Wnt inhibition. NCB-0846 shows inhibitory activity against TNIK with an half-maximal inhibitory concentration (IC50) value of 21 nM. It also inhibits FLT3, JAK3, PDGFRα, TRKA, CDK2/CycA2, and HGK (>80% at 0.1 μM). NCB-0846 induces faster migration of TCF4 phosphorylated by TNIK within a concentration range of 0.1-0.3 μM and completely inhibits the phosphorylation of TCF4 at a concentration of 3 μM. Furthermore, NCB-0846 blocks the auto-phosphorylation of TNIK. NCB-0846 inhibits the TCF/LEF transcriptional activity of Wnt3a-treated HEK293 and HCT116 (carrying CTNNB1 mutation) and DLD-1 (carrying APC mutation) colorectal cancer cells. NCB-0846 reduces the expression of the Wnt target genes AXIN2 and MYC as well as that of TNIK, but the expression of CCND1 is not affected. NCB-0846 also reduces the expression of TNIK, AXIN2 and cMYC at the protein level. LRP6 and LRP5 are also downregulated by NCB-0846. NCB-0846 can inhibit cancer cell growth in vitro. NCB-0846 induces an increase in the sub-G1 cell population. NCB-0846 can downregulate the expression of putative colorectal CSC markers: CD44, CD133, and aldehyde dehydrogenase-1 (ALDH1), and reduce the proportion of cells showing high expression of CSC surface markers (CD44, CD133, CD166, CD29 and EpCAM). NCB-0846 also reduces the expression of mesenchymal markers (Slug, Snail, Twist, Smad2 and Vimentin). However, embryonal stem cell markers (Oct4, Nanog and Sox2) are not affected[1].

In vivo NCB-0846 suppresses Wnt-driven intestinal tumorigenesis in Apcmin/+ mice and the sphere- and tumour-forming activities of colorectal cancer cells. The body weight of mice (immunodeficient tumor xenografts) falls at the beginning of NCB-0846 administration, but gradually recover. The expression of Wnt-target genes (AXIN2, MYC and CCND1) in xenografts is reduced following the administration of NCB-0846. NCB-0846 dose dependently reduces the multiplicity and dimensions of tumours that developed in the small intestine. NCB-0846 significantly suppresses the growth of the PDXs (patient-derived xenografts) established from the two patients in two more clinically relevant mouse models[1].


Cell Research:[1]
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  • Cell lines: HCT116 cells
  • Concentrations: 1 μM 
  • Incubation Time: 4 or 24 h
  • Method: HCT116 cells are cultured in the presence of DMSO (vehicle), 1 μM NCB-0846, or 1 μM NCB-0970 for 4 or 24 h and then analysed by immunoblotting with anti-phosphorylated TNIK, anti-TNIK, and anti-γ-tubulin (loading control) antibodies.
    (Only for Reference)
Animal Research:[1]
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  • Animal Models: Immunodeficient mice (background-BALB/c nude mice)
  • Formulation: DMSO/polyethylene glycol#400/30% 2-hydroxypropyl-β-cyclodextrin solution (10:45:45, v/v)
  • Dosages: 40 or 80 mg/kg BID
  • Administration: by oral gavage
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 75 mg/mL warmed (199.77 mM)
Ethanol 2 mg/mL warmed (5.32 mM)
Water Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 375.42


CAS No. 1792999-26-8
Storage powder
in solvent
Synonyms N/A

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID