NCB-0846

• CAT Number: I013674
• CAS Number: 1792999-26-8
• Molecular Formula: C21H21N5O2
• Molecular Weight: 375.42
• Purity: ≥95%
• Synonyms: 4-[2-(3H-benzimidazol-5-ylamino)quinazolin-8-yl]oxycyclohexan-1-ol
• InChI: InChI=1S/C21H21N5O2/c27-15-5-7-16(8-6-15)28-19-3-1-2-13-11-22-21(26-20(13)19)25-14-4-9-17-18(10-14)24-12-23-17/h1-4,9-12,15-16,27H,5-8H2,(H,23,24)(H,22,25,26)
• InChIKey: FYWRWBSYRGSWIQ-UHFFFAOYSA-N
• SMILES: C1CC(CCC1O)OC2=CC=CC3=CN=C(N=C32)NC4=CC5=C(C=C4)N=CN5

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

Reference

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