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

530758
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      Overview

      Replacement Information

      Key Specifications Table

      Empirical FormulaCAS #
      C₂₇H₂₁N₅O₂ 1469988-75-7

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      5.30758.0001
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          Glass bottle 5 mg
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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®
          Synonyms1-(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
          References
          ReferencesWu, H., et al. 2014. ACS Chem. Biol. 9, 1068.
          Product Information
          CAS number1469988-75-7
          FormYellow powder
          Hill FormulaC₂₇H₂₁N₅O₂
          Chemical formulaC₂₇H₂₁N₅O₂
          ReversibleN
          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

          References

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

          Technical Info

          Title
          White Paper: Further considerations of antibody validation and usage. (EMD)
          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
          Synonyms1-(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
          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.