CGI1746

製品コードS7051 バッチS705102

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C34H37N5O4
分子量 579.69 CAS No. 910232-84-7
Solubility (25°C)* 体外 DMSO 250 mg/mL (431.26 mM)
Ethanol (warmed with 50ºC water bath) 33 mg/mL (56.92 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.
* <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 CGI1746 is a potent and highly selective small-molecule inhibitor of the Btk with IC50 of 1.9 nM.
in vitro CGI1746 is specific for Btk, with ∼1,000-fold selectivity over Tec and Src family kinases. In an ATP-free competition binding assay, the dissociation constant for Btk is 1.5 nM. This compound inhibits Btk activity in a new binding mode that stabilizes an inactive nonphosphorylated enzyme conformation. It inhibits both auto- and transphosphorylation steps necessary for enzyme activation. This chemical completely inhibits anti-IgM–induced murine and human B cell proliferation, with IC50s of 134 nM and 42 nM, respectively, but had no effect on anti-CD3- and anti-CD28–induced T cell proliferation. It potently inhibits the proliferation of CD27+IgG+ B cells isolated from the tonsils of four human donors with an average IC50 of 112 nM. In macrophages, this compound abolishes FcγRIII-induced TNFα, IL-1β and IL-6 production. It potently inhibits TNFα, IL-1β and, to a lesser extent, IL-6 (three- to eight-fold higher IC50) production in human monocytes stimulated with immobilized or soluble immune complexes. [1]
in vivo CGI1746 abrogates B cell–dependent arthritis. This compound treatment (100 mg/kg, s.c, twice-daily dosing) results in significant inhibition (97%) of overall clinical arthritis scores. This compound treatment substantially reduces TNFα, IL-1β and IL-6, as well as MCP1 and MIP-1α on both the mRNA and protein level in the passive anti-collagen II antibody–induced arthritis (CAIA) model. This compound shows comparable efficacy to TNFα blockade and significantly reduces clinical scores, as well as joint inflammation, in mice or rats with established arthritis. [1]

プロトコル(参考用のみ)

キナーゼアッセイ Lanthascreen assay
Lanthascreen assay is performed at Km for ATP (10 μM) with human full-length Btk (C-terminal V5-His6 expressed in Sf9 cells) and quantified on an EnVision.

参考

  • https://pubmed.ncbi.nlm.nih.gov/21113169/

カスタマーフィードバック

Data from [Data independently produced by , , J Allergy Clin Immunol, 2017, 140(4):1054-1067]

Data from [Data independently produced by , , Biochem Biophys Res Commun, 2017, 483(1):230-236]

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：

Bruton's tyrosine kinase (BTK) and matrix metalloproteinase-9 (MMP-9) regulate NLRP3 inflammasome-dependent cytokine and neutrophil extracellular trap responses in primary neutrophils [ J Allergy Clin Immunol, 2025, 155(2):569-582] PubMed: 39547282
Differential impact of BTK active site inhibitors on the conformational state of full-length BTK [ Elife, 2020, 9e60470] PubMed: 33226337
Differential impact of BTK active site inhibitors on the conformational state of full-length BTK [ Elife, 2020, 9e60470] PubMed: 33226337
BTK induces CAM-DR through regulation of CXCR4 degradation in multiple myeloma. [ Am J Transl Res, 2019, 11(7):4139-4150] PubMed: 31396324
Human NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome activity is regulated by and potentially targetable through Bruton tyrosine kinase [Liu X J Allergy Clin Immunol, 2017, 140(4):1054-1067] PubMed: 28216434
The NLRP3 inflammasome and bruton's tyrosine kinase in platelets co-regulate platelet activation, aggregation, and in vitro thrombus formation. [Murthy P, et al. Biochem Biophys Res Commun, 2017, 483(1):230-236] PubMed: 28034752
Anti-tumor efficacy study of the Bruton's tyrosine kinase (BTK) inhibitor, ONO/GS-4059, in combination with the glycoengineered type II anti-CD20 monoclonal antibody obinutuzumab (GA101) demonstrates superior in vivo efficacy compared to ONO/GS-4059 in co䲧盌Ỵ盍㧀盋膉甘 [Yasuhiro T Leuk Lymphoma, 2017, 58(3):699-707] PubMed: 27684575
Autoinhibition of Bruton's tyrosine kinase (Btk) and activation by soluble inositol hexakisphosphate [ Elife, 2015, 4] PubMed: 25699547

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。

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