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    LFM-A13
    LFM-A13

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V0647
    CAS #: 244240-24-2Purity ≥98%

    Description: LFM-A13 (LFM-A1-3) is a novel, potent and specific Bruton's tyrosine kinase (BTK) inhibitor with potential anticancer activity. It inhibits BTK with an IC50 of 2.5 μM, and shows >100-fold selectivity over other protein kinases such as JAK1, JAK2, HCK, EGFR,and IRK. LFM-A13 inhibited recombinant BTK expressed in a baculovirus expression vector system. Besides its remarkable potency in BTK kinase assays, LFM-A13 was also found to be a highly specific inhibitor of Polo-like kinases. LFM-A13 shows high in vivo anticancer efficacy in BALB/c mice bearing BCL-1 leukemia.

    References: J Biol Chem. 1999 Apr 2;274(14):9587-99; Clin Cancer Res. 2002 May;8(5):1224-33; Am J Hematol. 2013 Jun;88(6):463-71. 

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    Molecular Weight (MW)360
    FormulaC11H8Br2N2O2
    CAS No.244240-24-2
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 72 mg/mL (200.0 mM)  
    Water: <1 mg/mL
    Ethanol: <1 mg/mL
    Other infoChemical Name: 2-Cyano-N-(2,5-dibromophenyl)-3-hydroxy-2-butenamide
    InChi Key: UVSVTDVJQAJIFG-VURMDHGXSA-N
    InChi Code: InChI=1S/C11H8Br2N2O2/c1-6(16)8(5-14)11(17)15-10-4-7(12)2-3-9(10)13/h2-4,16H,1H3,(H,15,17)/b8-6-
    SMILES Code: C/C(O)=C(C#N)/C(NC1=CC(Br)=CC=C1Br)=O
    SynonymsLFM-A13; LFM A13; LFM A13 


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    In Vitro

    In vitro activity: In BTK+ B-lineage leukemic cells, LFM-A13 enhances their sensitivity to ceramide- or vincristine-induced apoptosis. In BCL-1 cells, NALM-6 cells, or normal BALB/c splenocytes, LFM-13 inhibits the enzymatic activity of BTK in BCL-1 cells without affecting the BTK protein expression levels. In human neutrophils, LFM-A13 decreases the tyrosine phosphorylation induced by fMet-Leu-Phe and inhibits the production of superoxide anions and the stimulation of adhesion, chemotaxis, and phospholipase D activity.


    Kinase Assay: Purified His6-Plx1 (250 ng) is added to a 20 μL reaction mixture containing 1× kinase buffer (10 mM Tris-HCl, pH 7.5, 10 mM MgCl2, and 1 mM TT), 25 μM cold ATP, and 1 μCi [γ-32P]ATP in the presence of different concentrations of LFM-A13 ranging from 5 μg/mL (13.9 μM) to 100 μg/mL (278 μM). The reaction mixtures are incubated at room temperature for 15-30 min and autophosphorylation is stopped by addition of 2× SDS-PAGE reducing sample buffer. A parallel experiment is performed in the presence of cold ATP. The kinase reactions are then subjected to immunoblotting using the commercially available anti-Plk antibodies. The immunoblots confirmed that the same amount of Plx1 protein is present in each reaction. In addition, we also examined the effects of LFM-A13 on substrate phosphorylation by Plx1. In brief, 250 ng of purified Plx1 is first incubated at room temperature for one hour with different concentrations of LFM-A13. After one hour of incubation, the tubes containing the reaction mixtures are put on ice and the substrate, GST-Cdc25 peptide (254-316) (200 ng), kinase buffer, and [γ-32P]ATP are added and the kinase reaction allowed to proceed for 15 min at room temperature. Immunoblotting with anti-Cdc25 antibodies is used to confirm that equal amounts of the substrate peptide are present in each reaction mixture. Anti-Plk antibodies, the polyclonal antibodies to gluthathione-S-transferase (GST) and ECL kit are used in the assay. The mode of human PLK3 inhibition by LFM-A13 is examined in titration experiments using increasing concentrations of [γ-32P]ATP and purified N-terminal His6-tagged recombinant human PLK3, residues 19-301, expressed by baculovirus in Sf21 insect cells. In brief, in a final reaction volume of 25 μL, PLK3 (h) (5-10 mU) is incubated with 8 mM MOPS, pH 7.0, 0.2 mM EDTA, 2 mg/mL casein, 10 mM Mg acetate, and [γ-32P-ATP] (specific activity approx. 500 cpm/pmol, concentration as required). The reaction is initiated by the addition of the MgATP mix. After incubation for 40 min at room temperature, the reaction is stopped by the addition of 5 μL of a 3% phosphoric acid solution. Ten microliters of the reaction is then spotted onto a P30 filtermat and washed three times for 5 min in 75 mM phosphoric acid and once in methanol prior to drying and scintillation counting. The Ki of PLK3 by LFM-A13 is calculated from the reciprocal plots of the intensity of phosphorylation of the substrate (1/v) versus the concentration of the inhibitor (i) (viz., LFM-A13). From this Dixon plot, the Ki represents the dissociation constants of the EI complex, which is determined by the point of linear intersection. 


    Cell Assay: LFM-A13 (100 μM) suppresses Epo-induced phosphorylation of EpoR, Jak2, Btk, Stat5 and Erk1/2 in R10 cells. LFM-A13 (100 μM) inhibits auto-phosphorylation of Jak2, Tec and Btk rather than Lyn kinase auto-phosphorylation in COS cells. LFM-A13 potently inhibits Plx1 with IC50 of 10 μM; also inhibits BRK, BMX, FYN and with IC50s of 267, 281, 240 and 215 μM.

    In VivoIn BALB/c mice bearing BCL-1 leukemia, combination of LFM-A13 (50 mg/kg/day i.p.) and the standard triple-drug VPL prolongs the median survival time. In primary myeloma-bearing SCID-rab mice, LFM-A13 inhibits osteoclast activity, prevents myeloma-induced bone resorption and suppresss myeloma growth.
    Animal modelBALB/c mice bearing BCL-1 leukemia
    Formulation & Dosage50 mg/kg/day i.p.
    ReferencesJ Biol Chem. 1999 Apr 2;274(14):9587-99; Clin Cancer Res. 2002 May;8(5):1224-33; Am J Hematol. 2013 Jun;88(6):463-71. 


    These protocols are for reference only. InvivoChem does not independently validate these methods.

    LFM-A13

    Inhibition of BTK by shRNA or LFM-A13 impeded migration of primary myeloma cells toward SDF-1. Am J Hematol. 2013 Jun;88(6):463-71. 

    LFM-A13

    Inhibition of BTK impeded migration and homing of myeloma cells to bone in vivo. Am J Hematol.2013 Jun;88(6):463-71. 

    LFM-A13

    BTK expression was associated with cell-surface CXCR4, and BTK was phosphorylated (activated) by SDF-1 in myeloma cells. Am J Hematol. 2013 Jun;88(6):463-71. 


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