NCB-0846

NCB-0846 is an orally available TNIK inhibitor with an IC50 of 21 nM.

Signaling Pathways >> MAPK/ERK Pathway >> MAP4K

Signaling Pathways >> Stem Cell/Wnt >> Wnt

Research Areas >> Cancer

Wnt

TNIK:21 nM (IC50)

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[1].

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[1].

Mice: NCB-0846 is suspended in DMSO/polyethylene glycol#400/30% 2-hydroxypropyl-β-cyclodextrin solution (10:45:45v/v). Five million HCT116 cells suspended in medium containing 25% Matrigel are inoculated into the subcutaneous tissues of 9-week-old female BALB/c nude mice. Mice are randomized according to tumour volume (9 mice per group). NCB-0846 was administered daily by oral gavage at 0 (vehicle alone), 40 or 80 mg/kg (body weight) BID (bis in die) for 14 days[1].

[1]. Masuda M, et al. TNIK inhibition abrogates colorectal cancer stemness. Nat Commun. 2016 Aug 26;7:12586.

ICG-001 | Salinomycin | IWR-1 | Wnt-C59 | NG25 | Berberine chloride hydrate | Pyrvinium pamoate | ETC-159 | BML 284 | IWP-2 | Heparan Sulfate | GNE-495 | KYA 1797K | FH535 | SKL2001