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    InvivoChem Cat #: V4536
    CAS #: 2222355-77-1Purity ≥98%

    Description: SNIPER(ABL)-024 is a compound by conjugating GNF5 (an ABL inhibitor) to LCL161 derivative (IAP-inhibitor of apoptosis protein ligand) with a linker, induces the reduction of BCR-ABL protein with a DC50 of 5μM.Chromosomal translocation occurs in some cancer cells, which results in the expression of aberrant oncogenic fusion proteins that include BCR-ABL in chronic myelogenous leukemia (CML). Inhibitors of ABL tyrosine kinase, such as imatinib and dasatinib, exhibit remarkable therapeutic effects, although emergence of drug resistance hampers the therapy during long-term treatment. An alternative approach to treat CML is to downregulate the BCR-ABL protein. 

    References:  2017 Aug;108(8):1657-1666.

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    Molecular Weight: 1031.15
    Formula: C₅₂H₆₁F₃N₈O₉S
    CAS No.: 2222355-77-1
    SMILES: O=C(NCCOCCOCCOCCOC1=CC(C(C2=CSC([[email protected]]3N(C([[email protected]](C4CCCCC4)NC([[email protected]](C)NC)=O)=O)CCC3)=N2)=O)=CC=C1)C5=CC=CC(C6=NC=NC(NC7=CC=C(OC(F)(F)F)C=C7)=C6)=C5
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Technical InformationSNIPER(ABL)-024; SNIPER(ABL) 024

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    SNIPER(ABL)‐39 shows potent protein knockdown activity. (a) Chemical structures of SNIPER(ABL) with different linker length. (b) Effect of linker length on the protein knockdown activity of the SNIPER(ABL).  (c) Dose response of the protein knockdown activity of SNIPER(ABL)‐39. (d) Binding affinities of SNIPER(ABL)‐39 to ABL and IAP.


    SNIPER(ABL)‐39 inhibits proliferation of chronic myelogenous leukemia (CML) cells expressing native BCR‐ABL.  2017 Aug;108(8):1657-1666.


    SNIPER(ABL) composed of various ABL inhibitors and IAP ligands. (a) Chemical structures of SNIPER(ABL). (b–e) The protein knockdown activities of imatinib‐conjugated (b), GNF5‐conjugated (c), HG‐7‐85‐01‐conjugated (d) and dasatinib‐conjugated SNIPER(ABL) (e) were evaluated. K562 cells were incubated with the indicated concentration of SNIPER or ligands mix (LM; indicated ABL inhibitor and IAP ligand) for 6 h. Numbers below the ABL panel represent BCR‐ABL/GAPDH or BCR‐ABL/β‐tubulin ratio normalized by vehicle control as 100. (f) List of SNIPER(ABL) compounds and their DC 50 values. The upper name represents the code number of the SNIPER(ABL) and the lower number shows the concentration of SNIPER(ABL) required to reduce BCR‐ABL protein by 50% (DC 50, nM).  2017 Aug;108(8):1657-1666.


    Involvement of ubiquitin and IAP in SNIPER(ABL)‐39‐induced degradation of BCR‐ABL protein. (a) Turnover of BCR‐ABL proteins after SNIPER(ABL)‐39 treatment.  (b) Expression of Bcr‐Abl mRNA in K562 cells. (c) Effect of ubiquitin activating enzyme inhibitor MLN7243 on protein knockdown activity of SNIPER(ABL)‐39 in K562 cells. (d) Silencing of both cIAP1 and XIAP expression attenuates SNIPER(ABL)‐39‐dependent BCR‐ABL protein degradation.


    SNIPER(ABL)‐39 inhibits the BCR‐ABL‐related signaling pathway. K562 cells were incubated with the indicated concentration of SNIPER(ABL)‐39 or dasatinib for 6 h. pBCR‐ABL, pSTAT5 and pCrkL stand for phosphorylated BCR‐ABL, STAT5 and CrkL, respectively.  2017 Aug;108(8):1657-1666.


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