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Wnt&Beta catenin

NCB-0846 (1792999-26-8)

NCB-0846 is an orally available TNIK inhibitor with an IC50 of 21 nM. NCB-0846 is novel,first-in-class,orally TNIK inhibitor with an IC50 value of 21 nM,that have shown strong anti-tumor efficacy against several cancer models.

Not Intended for Therapeutic Use. For research use only.

CAS: 1792999-26-8 Category

NCB-0846 (1792999-26-8) Description

NCB-0846 is novel,first-in-class,orally TNIK inhibitor with an IC50 value of 21 nM,that have shown strong anti-tumor efficacy against several cancer models. NCB-0846 suppresses Wnt-driven intestinal tumorigenesis in Apcmin/+ mice and the sphere- and tumour-forming activities of colorectal cancer cells. NCB-0846 inhibits cancer cell growth in vitro and in vivo.NCB-0846 induced faster migration of TCF4 phosphorylated by TNIK within a concentration range of 0.1–0.3?μM and completely inhibited the phosphorylation of TCF4 at a concentration of 3?μM . Furthermore, NCB-0846 blocked the auto-phosphorylation of TNIK). NCB-0846 inhibited the TCF/LEF transcriptional activity of Wnt3a-treated HEK293 and HCT116 (carrying CTNNB1 mutation) and DLD-1 (carrying APC mutation) colorectal cancer cells. NCB-0846 reduced the expression of the Wnt target genes AXIN2 and MYC as well as that of TNIK, but the expression of CCND1 was not affected .NCB-0846 also reduced the expression of TNIK, AXIN2 and cMYC at the protein level. NCB-0846 showed 6.8-fold higher cell growth-inhibitory activity against HCT116 cells than NCB-0970. Meanwhile, compared with NCB-0970, NCB-0846 showed much higher (~20-fold) inhibitory activity against colony formation by the same cells in soft agar , indicating that this compound has more potent activity against the clonogenicity of cancer cells. NCB-0846 was administrable orally and suppressed the growth of tumours established by inoculating HCT116 cells into immunodeficient mice. The body weight of mice fell at the beginning of NCB-0846 administration, but gradually recovered.

 

NCB-0846 (1792999-26-8) Specifications

Product Name NCB-0846
Synonym NCB-0846
Chemical Name cis-4-(2-(3H-Benzo[d]imidazol-5-ylamino)quinazolin-8-yloxy)cyclohexanol
Drug Class N/A
Purity ≥ >98% (or refer to the Certificate of Analysis)
CAS Number 1792999-26-8
Molecular Formula C21H21N5O2
Molecular Weight 648.64
Monoisotopic Mass 375.17 g/mol
MDL number N/A
InChIKey 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 O[[email protected]]1CC[[email protected]@H](OC2=CC=CC3=CN=C(NC4=CC=C5N=CNC5=C4)N=C23)CC1
Form Solid powder
Color Off-White to Light Yellow
Solubility  Soluble in DMSO
Storage Temp.  0 – 4 C for short term (days to weeks), or -20 C for long term (months)
Shelf life > >2 years if stored properly
Handling Protect from air and light
Application NCB-0846 is a novel,first-in-class,orally TNIK inhibitor with an IC50 value of 21 nM,that have shown strong anti-tumor efficacy against several cancer models.

 


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