530758 BMX/BTK Inhibitor II, QL47 - CAS 1469988-75-7 - Calbiochem

530758
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Empirical FormulaCAS #
C₂₇H₂₁N₅O₂ 1469988-75-7

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      Description
      OverviewA cell-permeable tricyclic quinoline-acrylamide analog of BMX-IN-1 (Cat. No. 505021) that covalently modifies Cys481 in the kinase hinge region of Bruton's tyrosine kinase (BTK) and acts as a highly potent, selective, irreversible, and time-dependent inhibitor (IC50 = 6.6 nM). Also, inhibits the activity of bone marrow kinase on chromosome X (BMX) with equal potency (IC50 = 6.7 nM). Shown to be about 300-fold less potent against Cys496Ser mutated BTK. Displays excellent selectivity against a panel of 456 protein kinases, including JAK3, BLK, TEC, ITK, and EGFR and does not affect PI 3-K/mTOR and Raf/MEK/ERK signaling pathways. Diminishes autophosphorylation of BTK on Tyr223 in cells (EC50 = 475 nM) and promotes proteasome-mediated degradation of BTK (EC50 ~ 1 µM in HEK293T cells). Shown to induce cell cycle arrest at G1 phase and induce apoptotic cell death in Ramos cells. Also blocks the proliferation of several B-cell lymphoma cell lines (GI50 = 370, 200, 260,120, and 120 nM for Ramos, U2932, MM1S, RPMI8226, and BCWM.1, respectively).

      Please note that the molecular weight for this compound is batch-specific due to variable water content.
      Catalogue Number530758
      Brand Family Calbiochem®
      SynonymsBTK Inhibitor V, BLK Inhibitor II, 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
      References
      ReferencesWu, H., et al. 2014. ACS Chem. Biol. 9, 1068.
      Product Information
      CAS number1469988-75-7
      FormYellow powder
      Hill FormulaC₂₇H₂₁N₅O₂
      Chemical formulaC₂₇H₂₁N₅O₂
      ReversibleN
      Quality LevelMQ100
      Applications
      Biological Information
      Primary TargetBMX & BTK
      Purity≥98% by HPLC
      Physicochemical Information
      Cell permeableY
      Dimensions
      Materials Information
      Toxicological Information
      Safety Information according to GHS
      Safety Information
      Product Usage Statements
      Storage and Shipping Information
      Ship Code Ambient Temperature Only
      Toxicity Standard Handling
      Storage -20°C
      Do not freeze Ok to freeze
      Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
      Packaging Information
      Packaged under inert gas Packaged under inert gas
      Transport Information
      Supplemental Information
      Specifications

      Documentation

      BMX/BTK Inhibitor II, QL47 - CAS 1469988-75-7 - Calbiochem SDS

      Title

      Safety Data Sheet (SDS) 

      References

      Reference overview
      Wu, H., et al. 2014. ACS Chem. Biol. 9, 1068.
      Data Sheet

      Note that this data sheet is not lot-specific and is representative of the current specifications for this product. Please consult the vial label and the certificate of analysis for information on specific lots. Also note that shipping conditions may differ from storage conditions.

      Revision31-October-2014 JSW
      SynonymsBTK Inhibitor V, BLK Inhibitor II, 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
      DescriptionA 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.
      FormYellow powder
      Intert gas (Yes/No) Packaged under inert gas
      CAS number1469988-75-7
      Chemical formulaC₂₇H₂₁N₅O₂
      Purity≥98% by HPLC
      SolubilityGlacial acetic acid (2 mg/ml)
      Storage -20°C
      Do Not Freeze Ok to freeze
      Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
      Toxicity Standard Handling
      ReferencesWu, H., et al. 2014. ACS Chem. Biol. 9, 1068.