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NCB-0846

CAS No. : 1792999-26-8

產(chǎn)品活性：NCB-0846 is an orally available TNIK inhibitor with an IC₅₀ of 21?nM.

研究領(lǐng)域：Stem Cell/Wnt  |  MAPK/ERK Pathway

作用靶點(diǎn)：Wnt  |  MAP4K

In Vitro: NCB-0846 has anti-Wnt activity. 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 IC₅₀ of 21?nM. NCB-0846 also inhibits FLT3, JAK3, PDGFRα, TRKA, CDK2/CycA2, and HGK. 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. NCB-0846 inhibits HCT116 cell growth and shows much higher (-20-fold) inhibitory activity against colony formation by the same cells in soft agar.

In Vivo: NCB-0846 suppresses the growth of tumors established by inoculating HCT116 cells into immunodeficient mice. The expression of Wnt-target genes (AXIN2, MYC and CCND1) in xenografts is reduced following the administration of NCB-0846. NCB-0846 induces an increase in the sub-G1 cell population. Cleavage of poly (ADP-ribose) polymerase 1 indicates the induction of apoptosis.

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