NCB-0846

Cas：1792999-26-8

Product Information：

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.

Chemical Formula: C21H21N5O2

Exact Mass: 375.17

Molecular Weight: 375.43

Elemental Analysis: C, 67.18; H, 5.64; N, 18.65; O, 8.52

Synonym:

NCB-0846

NCB0846

NCB 0846

Chemical Name:

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

InChi Key: 

FYWRWBSYRGSWIQ-IYBDPMFKSA-N

InChi Code:

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+

Smiles Code:

O[C@H]1CC[C@@H](OC2=CC=CC3=CN=C(NC4=CC=C5N=CNC5=C4)N=C23)CC1

Technical Data：

Appearance: Solid powder

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

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

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.