NCB-0846

Catalog No.S8392 Batch:S839201

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Technical Data

Formula

C21H21N5O2
Molecular Weight 375.42 CAS No. 1792999-26-8
Solubility (25°C)* In vitro DMSO 75 mg/mL (199.77 mM)
Ethanol 2 mg/mL (5.32 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5% DMSO 95% Corn oil
0.37mg/ml Taking the 1 mL working solution as an example, add 50 μL of 7.4 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. 
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
3.75mg/ml Taking the 1 mL working solution as an example, add 50 μL of 75 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description NCB-0846 is a novel, orally small-molecule Wnt inhibitor that inhibits TNIK (TRAF2 and NCK-Interacting Kinase, MAP4K7) with an IC50 value of 21 nM.
Targets
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].

Protocol (from reference)

Cell Assay:[1]
  • 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.

Animal Study:[1]
  • Animal Models

    Immunodeficient mice (background-BALB/c nude mice)

  • Dosages

    40 or 80 mg/kg BID

  • Administration

    by oral gavage

Selleck's NCB-0846 has been cited by 4 publications

Establishment and characterization of immortalized sweat gland myoepithelial cells [ Sci Rep, 2022, 12(1):7] PubMed: 34997030
TNIK Inhibition Has Dual Synergistic Effects on Tumor and Associated Immune Cells [ Adv Biol (Weinh), 2022, 6(8):e2200030] PubMed: 35675910
Characterization of the ERG-regulated Kinome in Prostate Cancer Identifies TNIK as a Potential Therapeutic Target [ Neoplasia, 2019, 21(4):389-400] PubMed: 30901730
The transcriptional coactivator WBP2 primes triple-negative breast cancer cells for responses to Wnt signaling via the JNK/Jun kinase pathway [ J Biol Chem, 2018, 293(52):20014-20028] PubMed: 30442712

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.