NCB-0846

製品コードS8392 バッチS839201

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₂₁H₂₁N₅O₂

分子量

375.42

CAS No.

1792999-26-8

Solubility (25°C)*

体外

DMSO (warmed with 50ºC water bath)

75 mg/mL (199.77 mM)

Ethanol (warmed with 50ºC water bath)

2 mg/mL (5.32 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

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 この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	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 この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	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.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	NCB-0846は、IC50値21 nMでTNIK (TRAF2 and NCK-Interacting Kinase, MAP4K7)を阻害する、新規の経口小分子Wnt阻害剤です。
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.
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.

プロトコル(参考用のみ)

細胞アッセイ	細胞株	HCT116 cells
	濃度	1 μM
	反応時間	4 or 24 h
	実験の流れ	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.
動物実験	動物モデル	Immunodeficient mice (background-BALB/c nude mice)
	投薬量	40 or 80 mg/kg BID
	投与方法	by oral gavage

参考

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

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

The EIF3H-HAX1 axis increases RAF-MEK-ERK signaling activity to promote colorectal cancer progression [ Nat Commun, 2024, 15(1):2551]	PubMed: 38514606
The Traf2 and NcK interacting kinase inhibitor NCB-0846 suppresses seizure activity involving the decrease of GRIA1 [ Genes Dis, 2024, 11(3):100997]	PubMed: 38292191
Establishment and characterization of immortalized sweat gland myoepithelial cells [ Sci Rep, 2022, 12(1):7]	PubMed: 34997030
TNIK Inhibition Has Dual Synergistic Effects on Tumor and Associated Immune Cells [ Adv Biol (Weinh), 2022, 6(8):e2200030]	PubMed: 35675910
Characterization of the ERG-regulated Kinome in Prostate Cancer Identifies TNIK as a Potential Therapeutic Target [ Neoplasia, 2019, 21(4):389-400]	PubMed: 30901730
The transcriptional coactivator WBP2 primes triple-negative breast cancer cells for responses to Wnt signaling via the JNK/Jun kinase pathway [ J Biol Chem, 2018, 293(52):20014-20028]	PubMed: 30442712

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。