Basic Description

Synonyms	Cyclohexanol,4-[[2-(1H-benzimidazol-6-ylamino)-8-quinazolinyl]oxy]-,cis-
Specifications & Purity	≥99%
Biochemical and Physiological Mechanisms	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.
Storage Temp	Store at -20°C
Shipped In	Ice chest + Ice pads This product requires cold chain shipping. Ground and other economy services are not available.
Product Description	Information 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. Targets TNIK (Cell-free assay) 21 nM In vitro NCB-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 vivo NCB-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

Taxonomic Classification

Taxonomy Tree

Kingdom Organic compounds
- Superclass Organoheterocyclic compounds
  - Class Diazanaphthalenes
    - Subclass Benzodiazines
      - Level5 Quinazolines
        Level6 Quinazolinamines

Kingdom	Organic compounds
Superclass	Organoheterocyclic compounds
Class	Diazanaphthalenes
Subclass	Benzodiazines
Intermediate Tree Nodes	Quinazolines
Direct Parent	Quinazolinamines
Alternative Parents	Benzimidazoles Cyclohexanols Aminopyrimidines and derivatives Alkyl aryl ethers Benzenoids Imidazoles Heteroaromatic compounds Cyclic alcohols and derivatives Secondary amines Azacyclic compounds Organopnictogen compounds Hydrocarbon derivatives
Molecular Framework	Aromatic heteropolycyclic compounds
Substituents	Quinazolinamine - Benzimidazole - Cyclohexanol - Aminopyrimidine - Alkyl aryl ether - Benzenoid - Pyrimidine - Heteroaromatic compound - Imidazole - Cyclic alcohol - Azole - Secondary alcohol - Azacycle - Secondary amine - Ether - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Hydrocarbon derivative - Organooxygen compound - Organonitrogen compound - Amine - Alcohol - Aromatic heteropolycyclic compound
Description	This compound belongs to the class of organic compounds known as quinazolinamines. These are heterocyclic aromatic compounds containing a quianazoline moiety substituted by one or more amine groups.
External Descriptors	Not available
1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61. DOI: 10.1186/s13321-016-0174-y

Associated Targets(Human)

TNIK Tchem TRAF2- and NCK-interacting kinase (1174 Activities)

Discover Target: TNIK

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

U2OS (164939 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

HCT-116 (91556 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Mechanisms of Action

Mechanism of Action	Action Type	target ID	Target Name	Target Type	Target Organism	Binding Site Name	References

Names and Identifiers

IUPAC Name	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
Isomeric SMILES	C1CC(CCC1O)OC2=CC=CC3=CN=C(N=C32)NC4=CC5=C(C=C4)N=CN5
Molecular Weight	375.42
Reaxy-Rn	37092003
Reaxys-RN_link_address	https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=37092003&ln=

Certificates（CoA,COO,BSE/TSE and Analysis Chart)

C of A & Other Certificates(BSE/TSE, COO):

Analytical Chart:

Chemical and Physical Properties

Solubility	Solubility (25°C) In vitro DMSO: 75 mg/mL warmed with 50ºC Water: bath (199.77 mM); Ethanol: 2 mg/mL warmed with 50ºC Water: bath (5.32 mM); Water: Insoluble;
Molecular Weight	375.400 g/mol
XLogP3	3.600
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	4
Exact Mass	375.17 Da
Monoisotopic Mass	375.17 Da
Topological Polar Surface Area	96.000 Å²
Heavy Atom Count	28
Formal Charge	0
Complexity	515.000
Isotope Atom Count	0
Defined Atom Stereocenter Count	0
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
The total count of all stereochemical bonds	0
Covalently-Bonded Unit Count	1

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SKU	Size	Availability	Price	Qty
N413998-5mg	5mg	Available within 8-12 weeks(?) Production requires sourcing of materials. We appreciate your patience and understanding.	$88.90
N413998-25mg	25mg	Available within 8-12 weeks(?) Production requires sourcing of materials. We appreciate your patience and understanding.	$315.90

NCB-0846 - 99%, high purity , CAS No.1792999-26-8