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NCB-0846 MAP4K inhibitor

Name: NCB-0846
Brand: Selleck Chemicals
SKU: S8392
Availability: InStock
Rating: 5 (6 reviews)

Catalog No.S8392 Purity:99.61%

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.

Chemical Structure

Molecular Weight: 375.42

Purity & Quality Control

Batch: S839201 DMSO]75 mg/mL]false]Ethanol]2 mg/mL]false]Water]Insoluble]false Purity: 99.61%

99.61

Related Products

Related Targets	MAP4K2 MAP4K4 MAP4K6 MAP4K7	Click to Expand
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Related Compound Libraries	FDA-approved Drug Library Natural Product Library Bioactive Compound Library-I Highly Selective Inhibitor Library Express-Pick Library	Click to Expand

Mechanism of Action

Targets

TNIK ^[1]
(Cell-free assay)

21 nM

In vitro
In vitro	NCB-0846 blocks Wnt signalling and shows marked anti-tumour and anti-CSC activities. This compound binds to TNIK in an inactive conformation, and this binding mode seems to be essential for Wnt inhibition. It shows inhibitory activity against TNIK with an half-maximal inhibitory concentration (IC50) value of 21 nM. It also inhibits FLT3, JAK3, PDGFRα, TRKA, CDK2/CycA2, and HGK (>80% at 0.1 μM). This chemical 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. Furthermore, it blocks the auto-phosphorylation of TNIK. It inhibits the TCF/LEF transcriptional activity of Wnt3a-treated HEK293 and HCT116 (carrying CTNNB1 mutation) and DLD-1 (carrying APC mutation) colorectal cancer cells. This compound 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. It also reduces the expression of TNIK, AXIN2 and cMYC at the protein level. LRP6 and LRP5 are also downregulated by this chemical. It can inhibit cancer cell growth in vitro. This compound induces an increase in the sub-G1 cell population. It 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). It 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^[1].
Cell Research	Cell lines	HCT116 cells
	Concentrations	1 μM
	Incubation Time	4 or 24 h
	Method	HCT116 cells are cultured in the presence of DMSO (vehicle), 1 μM NCB-0846, or 1 μM this compound for 4 or 24 h and then analysed by immunoblotting with anti-phosphorylated TNIK, anti-TNIK, and anti-γ-tubulin (loading control) antibodies.

In Vivo
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 this compound administration, but gradually recover. The expression of Wnt-target genes (AXIN2, MYC and CCND1) in xenografts is reduced following the administration of this compound. This compound dose dependently reduces the multiplicity and dimensions of tumours that developed in the small intestine. It significantly suppresses the growth of the PDXs (patient-derived xenografts) established from the two patients in two more clinically relevant mouse models^[1].
Animal Research	Animal Models	Immunodeficient mice (background-BALB/c nude mice)
	Dosages	40 or 80 mg/kg BID
	Administration	by oral gavage

References

http://www.nature.com/articles/ncomms12586

Chemical Information

Molecular Weight	375.42	Formula	C₂₁H₂₁N₅O₂
CAS No.	1792999-26-8	SDF	Download SDF
Synonyms	N/A
Smiles	C1CC(CCC1O)OC2=CC=CC3=CN=C(N=C32)NC4=CC5=C(C=C4)N=CN5

Storage and Stability

Storage (From the date of receipt)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
			1 month-20°Cin solvent

In vitro
Batch:

DMSO : 75 mg/mL ( (199.77 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 2 mg/mL

Water : Insoluble

Molecular Weight Calculator

In vivo Batch: Add solvents to the product individually and in order.				In vivo Formulation Calculator
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	3.750mg/ml (9.99mM)	Taking the 1 mL working solution as an example, add 50 μL of 75 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.370mg/ml (0.99mM)	Taking the 1 mL working solution as an example, add 50 μL of 7.4 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

Preparing Stock Solutions

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
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Dilution Calculator Molecular Weight Calculator

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

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