NCB-0846 (C008B-271209)

NCB-0846 NCB-0846 is a novel, orally small-molecule Wnt inhibitor that inhibits TNIK (TRAF2 and NCK-Interacting Kinase, MAP4K7) with an IC50 value of 21 nM.TargetsTNIK (Cell-free assay) 21 nMIn vitroNCB-0846 blocks Wnt signalling and shows marked anti-tumour and anti-CSC activities. 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 half-maximal inhibitory concentration (IC50) value of 21\u2009nM. It also inhibits FLT3, JAK3, PDGFRα, TRKA, CDK2/CycA2, and HGK (>80% at 0.1\u2009μM). NCB-0846 induces faster migration of TCF4 phosphorylated by TNIK within a concentration range of 0.1-0.3\u2009μM and completely inhibits the phosphorylation of TCF4 at a concentration of 3\u2009μM. Furthermore, NCB-0846 blocks the auto-phosphorylation of TNIK. NCB-0846 inhibits 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 reduces the expression of the Wnt target genes AXIN2 and MYC as well as that of TNIK, but the expression of CCND1 is not affected. NCB-0846 also reduces the expression of TNIK, AXIN2 and cMYC at the protein level. LRP6 and LRP5 are also downregulated by NCB-0846. NCB-0846 can inhibit cancer cell growth in vitro. NCB-0846 induces an increase in the sub-G1 cell population. NCB-0846 can downregulate the expression of putative colorectal CSC markers: CD44, CD133, and aldehyde dehydrogenase-1 (ALDH1), and reduce the proportion of cells showing high expression of CSC surface markers (CD44, CD133, CD166, CD29 and EpCAM). NCB-0846 also reduces the expression of mesenchymal markers (Slug, Snail, Twist, Smad2 and Vimentin). However, embryonal stem cell markers (Oct4, Nanog and Sox2) are not affected.In vivoNCB-0846 suppresses Wnt-driven intestinal tumorigenesis in Apcmin/+ mice and the sphere- and tumour-forming activities of colorectal cancer cells. The body weight of mice (immunodeficient tumor xenografts) falls at the beginning of NCB-0846 administration, but gradually recover. The expression of Wnt-target genes (AXIN2, MYC and CCND1) in xenografts is reduced following the administration of NCB-0846. NCB-0846 dose dependently reduces the multiplicity and dimensions of tumours that developed in the small intestine. NCB-0846 significantly suppresses the growth of the PDXs (patient-derived xenografts) established from the two patients in two more clinically relevant mouse models.Cell Research(from reference)Cell lines：HCT116 cells Concentrations：1\u2009μM\xa0 Incubation Time：4 or 24\u2009h

MAP4K Inhibitors

Specifications & Purity: NCB-0846 NCB-0846 is a novel, orally small-molecule Wnt inhibitor that inhibits TNIK (TRAF2 and NCK-Interacting Kinase, MAP4K7) with an IC50 value of 21 nM.TargetsTNIK (Cell-free assay) 21 nMIn vitroNCB-0846 blocks Wnt signalling and shows marked anti-tumour and anti-CSC activities. 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 half-maximal inhibitory concentration (IC50) value of 21\u2009nM. It also inhibits FLT3, JAK3, PDGFRα, TRKA, CDK2/CycA2, and HGK (>80% at 0.1\u2009μM). NCB-0846 induces faster migration of TCF4 phosphorylated by TNIK within a concentration range of 0.1-0.3\u2009μM and completely inhibits the phosphorylation of TCF4 at a concentration of 3\u2009μM. Furthermore, NCB-0846 blocks the auto-phosphorylation of TNIK. NCB-0846 inhibits 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 reduces the expression of the Wnt target genes AXIN2 and MYC as well as that of TNIK, but the expression of CCND1 is not affected. NCB-0846 also reduces the expression of TNIK, AXIN2 and cMYC at the protein level. LRP6 and LRP5 are also downregulated by NCB-0846. NCB-0846 can inhibit cancer cell growth in vitro. NCB-0846 induces an increase in the sub-G1 cell population. NCB-0846 can downregulate the expression of putative colorectal CSC markers: CD44, CD133, and aldehyde dehydrogenase-1 (ALDH1), and reduce the proportion of cells showing high expression of CSC surface markers (CD44, CD133, CD166, CD29 and EpCAM). NCB-0846 also reduces the expression of mesenchymal markers (Slug, Snail, Twist, Smad2 and Vimentin). However, embryonal stem cell markers (Oct4, Nanog and Sox2) are not affected.In vivoNCB-0846 suppresses Wnt-driven intestinal tumorigenesis in Apcmin/+ mice and the sphere- and tumour-forming activities of colorectal cancer cells. The body weight of mice (immunodeficient tumor xenografts) falls at the beginning of NCB-0846 administration, but gradually recover. The expression of Wnt-target genes (AXIN2, MYC and CCND1) in xenografts is reduced following the administration of NCB-0846. NCB-0846 dose dependently reduces the multiplicity and dimensions of tumours that developed in the small intestine. NCB-0846 significantly suppresses the growth of the PDXs (patient-derived xenografts) established from the two patients in two more clinically relevant mouse models.Cell Research(from reference)Cell lines：HCT116 cells Concentrations：1\u2009μM\xa0 Incubation Time：4 or 24\u2009h

Grade: Moligand™

Molecular Formula: C21H21N5O2

Molecular Weight: 375.42

PubChem CID: 91801204

Isomeric SMILES: C1CC(CCC1O)OC2=CC=CC3=CN=C(N=C32)NC4=CC5=C(C=C4)N=CN5

Storage Temperature: Store at -20°C

Shipped in: Ice chest + Ice pads

UPC:

51442714

Weight:

1.06 Ounces

HazmatClass:

Yes

Quantity:

1

Unit of Measurement:

EA

WeightUOM:

LB

MPN:

N413998-1mg

Country of Origin:

China

CAS:

1792999-26-8

Product Size:

1mg

Harmonized Tariff Code:

2931.90.90