CGI1746

製品コードS7051 バッチS705101

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 100 mg/mL (172.5 mM)
Ethanol 100 mg/mL warmed with 50ºC water bath (172.5 mM)
Water 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 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. CGI1746 inhibits Btk activity in a new binding mode that stabilizes an inactive nonphosphorylated enzyme conformation. CGI1746 inhibits both auto- and transphosphorylation steps necessary for enzyme activation. CGI1746 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. CGI1746 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, CGI1746 abolishes FcγRIII-induced TNFα, IL-1β and IL-6 production. CGI1746 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. CGI1746 treatment (100 mg/kg, s.c, twice-daily dosing) results in significant inhibition (97%) of overall clinical arthritis scores. CGI1746 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. CGI1746 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.

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：

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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