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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C34H37N5O4 |
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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. |
製品説明 | CGI1746 is a potent and highly selective small-molecule inhibitor of the Btk with IC50 of 1.9 nM. |
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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] |
キナーゼアッセイ | Lanthascreen assay | |
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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. |
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]
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。
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。