NCB-0846

NCB-0846 is the first orally available small-molecule TNIK inhibitor, having anti-Wnt activity and suppressing Wnt-driven intestinal tumorigenesis, also inhibiting FLT3, JAK3, PDGFRa, TRKA, CDK2/CycA2, and HGK.

Product information

CAS Number: 1792999-26-8

Molecular Weight: 375.42

Formula: C21H21N5O2

Synonym:

NCB 0846

NCB0846

Chemical Name: cis-4-(2-(3H-Benzo[d]imidazol-5-ylamino)quinazolin-8-yloxy)cyclohexanol

Smiles: O[C@@H]1CC[C@@H](CC1)OC1=CC=CC2=CN=C(NC3=CC=C4N=CNC4=C3)N=C12

InChiKey: FYWRWBSYRGSWIQ-IYBDPMFKSA-N

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)/t15-,16+

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

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.

References:

1. Yamada T, Masuda M. Emergence of TNIK inhibitors in cancer therapeutics. Cancer Sci. 2017 May;108(5):818-823. doi: 10.1111/cas.13203. Epub 2017 Apr 24. Review. PubMed PMID: 28208209; PubMed Central PMCID: PMC5448614.
2. Masuda M, Uno Y, Ohbayashi N, Ohata H, Mimata A, Kukimoto-Niino M, Moriyama H, Kashimoto S, Inoue T, Goto N, Okamoto K, Shirouzu M, Sawa M, Yamada T. TNIK inhibition abrogates colorectal cancer stemness. Nat Commun. 2016 Aug 26;7:12586. doi: 10.1038/ncomms12586. PubMed PMID: 27562646; PubMed Central PMCID: PMC5007443.

Products are for research use only. Not for human use.