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Purity: = 99.52%
NCB-0846 (NCB0846) is a novel, first orally bioavailable small molecule inhibitor of Wnt that inhibits TNIK (TRAF2 and NCK-Interacting Kinase) with IC50 value of 21 nM. Canonical Wnt/β-catenin signalling is essential for maintaining intestinal stem cells, and its constitutive activation has been implicated in colorectal carcinogenesis. NCB-0846 binds to TNIK in an inactive conformation, and this binding mode seems to be essential for Wnt inhibition. NCB-0846 suppresses Wnt-driven intestinal tumorigenesis in Apc(min/+) mice and the sphere- and tumour-forming activities of colorectal cancer cells. TNIK is required for the tumour-initiating function of colorectal cancer stem cells, therefore the inhibition of TNIK by NCB-0846 may be a promising therapeutic approach.
| ln Vitro |
NCB-0846 exhibits anti-Wnt properties. TNIK is bound by NCB-0846 in an inactive conformation; this binding mode seems to be essential for Wnt suppression. With an IC50 of 21 nM, NCB-0846 has inhibitory action against TNIK. Moreover, FLT3, JAK3, PDGFRα, TRKA, CDK2/CycA2, and HGK are inhibited by NCB-0846. At concentrations between 0.1 and 0.3 μM, NCB-0846 accelerates the migration of TNIK-phosphorylated TCF4, and at 3 μM, it totally prevents TCF4 phosphorylation. In addition to inhibiting HCT116 cell growth, NCB-0846 has a greater (-20-fold) inhibitory action when it comes to the same cells' ability to form colonies in soft agar [1].
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| ln Vivo |
The formation of tumors created by grafting HCT116 cells into immunocompromised mice is inhibited by NCB-0846. Wnt target gene expression (AXIN2, MYC, and CCND1) was downregulated in xenografts following NCB-0846 treatment. There is an increase in sub-G1 cell populations caused by NCB-0846. Apoptosis is induced when poly(ADP-ribose) polymerase 1 cleaves [1].
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| References |
[1]. Masuda M, et al. TNIK inhibition abrogates colorectal cancer stemness. Nat Commun. 2016 Aug 26;7:12586
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| Molecular Formula |
C21H21N5O2
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| Molecular Weight |
375.42
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| CAS # |
1792999-26-8
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| SMILES |
O[ C@H]1CC[C@@H](OC2=CC=CC3=CN=C(NC4=CC=C5N=CNC5=C4)N=C23)CC1
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.25 mg/mL (5.99 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 22.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.25 mg/mL (5.99 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 22.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6637 mL | 13.3184 mL | 26.6368 mL | |
| 5 mM | 0.5327 mL | 2.6637 mL | 5.3274 mL | |
| 10 mM | 0.2664 mL | 1.3318 mL | 2.6637 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Reduced tumorigenicity ofTnik-deficient mice.Nat Commun.2016 Aug 26;7:12586. |
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Identification of a novel TNIK inhibitor.Nat Commun.2016 Aug 26;7:12586. |
NCB-0846inhibits cancer cell growthin vitroandin vivo.Nat Commun.2016 Aug 26;7:12586. |
Structural basis of TNIK inhibition.Nat Commun.2016 Aug 26;7:12586. |
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TNIK inhibition abrogates colorectal cancer stemness.Nat Commun.2016 Aug 26;7:12586. |
Patient-derived cancer-initiating cells.Nat Commun.2016 Aug 26;7:12586. |
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