Takinib (EDHS-206)

製品コードS8663 バッチS866301

化学情報

	Synonyms	EDHS-206	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₁₈H₁₈N₄O₂
	分子量	322.36	CAS No.	1111556-37-6
Solubility (25°C)*	体外	DMSO	30 mg/mL (93.06 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <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	Takinibは、IC50が9.5 nMの強力で選択的なTAK1阻害剤であり、2番目および3番目にランク付けされたターゲットであるIRAK4（120 nM）およびIRAK1（390 nM）よりもそれぞれ1.5 log以上強力です。Takinibはアポトーシスを誘発します。
in vitro	Takinib is an inhibitor of autophosphorylated and non-phosphorylated TAK1 that binds within the ATP-binding pocket and inhibits by slowing down the rate-limiting step of TAK1 activation. At 10 μM, this compound shows significant inhibitory activity (<10% enzyme activity after exposure) on six serine/threonine kinases, including TAK1, IRAK4, IRAK1, GCK, CLK2, and MINK1. TAK1/MAP3K7 is most potently inhibited with a half maximal inhibitory concentration (IC50) value of 9.5 nM. In cell models of rheumatoid arthritis and metastatic breast cancer, this inhibitor treatment results in TNF-a-dependent induction of apoptosis due to inhibition of TAK1 as a key switch between survival and cell death. It does not inhibit any of the MAP2Ks or MAP3Ks family members, i.e., MKK6/MAP2K6, MEKK1/ MAP3K1, MKK1/MAP2K1. This chemical also shows no efficacy toward the TAK1-closely related MAP3K5/ASK1. It potently and selectively targets TAK1 and induces apoptosis in TNF-a-stimulated breast cancer and RA in vitro models.
in vivo	This compound slows tumor growth in the Hodgkin lymphoma xenograft NSG mice.

プロトコル(参考用のみ)

細胞アッセイ	細胞株	MDA-MB-231 cells
	濃度	--
	反応時間	24 h
	実験の流れ	MDA-MB-231 cells (1,000 cells/well) are seeded in a 96-well plate with 10% FBS, 5% Pen/Strep, 4g/l glucose DMEM medium. After 24h, cells are serum starved with 1% FBS, 5% Pen/Strep, 4g/l glucose DMEM medium for 4h. Cells are treated with titrations of this compound in the presence or absence of 30 ng/mL TNFa. Plates at 0h and 24h following treatment were frozen at -80℃ after removal of media. After 24h, 100 μl ddH2O is added to each well and plates are refrozen. 1 μl from Hoechst stock [1 mg/ml in 1:4 DMSO/H2O] is dissolved in 1 ml of TNE buffer (10mM Tris, 2M NaCl, 1 mM Na2EDTA) and 100 μl of this solution is added to each well. The fluorescence is determined at 355/460 nm.
動物実験	動物モデル	Female NSG mice
	投薬量	50 mg/kg
	投与方法	p.o.

参考

https://pubmed.ncbi.nlm.nih.gov/28820959/
https://pubmed.ncbi.nlm.nih.gov/33139544/

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：

ADP-heptose attenuates Helicobacter pylori-induced dendritic cell activation [ Gut Microbes, 2024, 16(1):2402543]	PubMed: 39288239
Deciphering the toxicity of polyhexamethylene guanidine phosphate in lung carcinogenesis: Mutational profiles and molecular mechanisms [ Chemosphere, 2024, 368:143785]	PubMed: 39577803
In vivo induction of activin A-producing alveolar macrophages supports the progression of lung cell carcinoma [ Nat Commun, 2023, 14(1):143]	PubMed: 36650150
Takinib inhibits microglial M1 polarization and oxidative damage after subarachnoid hemorrhage by targeting TAK1-dependent NLRP3 inflammasome signaling pathway [ Front Immunol, 2023, 14:1266315]	PubMed: 38035075
ATP/IL-33-Co-Sensing by Mast Cells (MCs) Requires Activated c-Kit to Ensure Effective Cytokine Responses [ Cells, 2023, 12(23)2696]	PubMed: 38067124
TAK1 Reduces Surgery-induced Overactivation of RIPK1 to Relieve Neuroinflammation and Cognitive Dysfunction in Aged Rats [ Neurochem Res, 2023, 10.1007/s11064-023-03959-z]	PubMed: 37329446
Androgen Receptor Regulation in Prostate Stroma [ THE UNIVERSITY OF ARIZONA, 2023, ]	PubMed: none
FAK mediates LPS-induced inflammatory lung injury through interacting TAK1 and activating TAK1-NFκB pathway [ Cell Death Dis, 2022, 13(7):589]	PubMed: 35803916
Inhibition of Protein Synthesis Induced by CHK1 Inhibitors Discriminates Sensitive from Resistant Cancer Cells [ ACS Pharmacol Transl Sci, 2021, 4(4):1449-1461]	PubMed: 34423276
A role for SHARPIN in platelet linear protein ubiquitination and function [ bioRxiv, 2021, 10.1101/2021.01.13.426403]	PubMed: None

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。