5.30758

BMX/BTK Inhibitor II, QL47

• Sinônimo(s): BMX/BTK Inhibitor II, QL47, 1-(1-Acryloylindolin-6-yl)-9-(1-methyl-1H-pyrazol-4-yl)benzo[h][1,6]naphthyridin-2(1H)-one, BMX Inhibitor II, TEC Inhibitor II, Brutonʹs Tyrosine Kinase Inhibitor V, PI 3-K Inhibitor XXI, BTK Inhibitor V, BLK Inhibitor II
• Fórmula empírica (Notação de Hill): C₂₇H₂₁N₅O₂
• Número CAS: 1469988-75-7
• Peso molecular: 447.49
• Número MDL: MFCD22124682
• Código UNSPSC: 12352200
• NACRES: NA.77

Propriedades

• Ensaio: ≥98% (HPLC)
• Nível de qualidade: 100
• Formulário: powder
• fabricante/nome comercial: Calbiochem^®
• condição de armazenamento: OK to freeze
• cor: yellow
• solubilidade: glacial acetic acid: 2 mg/mL
• temperatura de armazenamento: −20°C
• cadeia de caracteres SMILES: [n]1(ncc(c1)c2cc3c4[n]([c](ccc4cnc3cc2)=O)c5cc6c(cc5)CCN6C(=O)C=C)C
• InChI: 1S/C27H21N5O2/c1-3-25(33)31-11-10-17-4-7-21(13-24(17)31)32-26(34)9-6-19-14-28-23-8-5-18(12-22(23)27(19)32)20-15-29-30(2)16-20/h3-9,12-16H,1,10-11H2,2H3
• chave InChI: RTRNJQOBEOISFQ-UHFFFAOYSA-N

Descrição

Descrição geral

A cell-permeable, BMX-IN-1 (Cat. No. 505021 ) family of acrylamide-containing tricyclic quinoline that acts as a dual BMX & BTK inhibitor (IC₅₀ = 6.7 & 6.6 nM, respectively) by targeting ATP-binding site and covalently modifying kinase hinge cysteine (Cys481 in human BTK) with its eletrophilic acrylamide, while inhibiting TEC, BLK, PI 3-K kinase activity only at higher concentrations (IC₅₀ = 195, 366, and 696 nM, respectively) and exhibiting much reduced or no potency against 29 other kinases (IC₅₀ ≥ 1.2 µM). Likewise, potent inhibition is only seen with BTK in an affinity-based selectivity profiling among a panel of 456 kinases. Shown to effectively inhibit anti-IgM-stimulated BTK Y223 autophosphorylation and downstream effector PLCγ2 Y759 phosphorylation (IC₅₀ = 475 & 318 nM, respectively) without affecting the phosphorylation of upstream kinase Syk, nor S6K and Erk from the PI 3-K/mTOR and Raf/Mek/Erk signaling pathway, respectively. More effective than PCI-32765 (ibrutinib) in inducing PARP & Caspase-3 cleavage in Ramos cultures (Effective conc. <5 µM vs. >10 µM; 8 h) and is more potent than AVL-292, BMX-IN-1, CGI-1746, PCI-32765 in antiproliferation activity against 8 B-cell cancer cell lines (GI₅₀ ranges from 120 to 490 nM; 4.9- and 10.8-fold of BMX-IN-1 potency in Ramos and U2932 cultures, respectively). In addition to loss of kinase activity, irreversible inhibitor-modified BTK via Cys481 covalent bond formation is reported to exhibit shortened cellular half-life. Due to poor microsomal stability, QL47 is not recommended for in vivo studies.

Ações bioquímicas/fisiológicas

Cell permeable: yes

Primary Target
BMX & BTK

Reversible: no

Embalagem

Packaged under inert gas

Advertência

Toxicity: Standard Handling (A)

Reconstituição

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Outras notas

Wu, H., et al. 2014. ACS Chem. Biol.9, 1068.

Informações legais

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Informações de segurança

• Código de classe de armazenamento: 11 - Combustible Solids
• Classe de risco de água (WGK): WGK 3
• Ponto de fulgor (°F): Not applicable
• Ponto de fulgor (°C): Not applicable