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    Selinexor (KPT-330)
    Selinexor (KPT-330)

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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 #: V1589
    CAS #: 1393477-72-9Purity ≥98%

    Description: This product has been discontinued. Selinexor (also known as KPT-330) is an orally bioavailable, potent and  selective CRM1 inhibitor. Selinexor is effective in acquired resistance to ibrutinib and synergizes with ibrutinib in chronic lymphocytic leukemia. Selinexor potentiates the antitumor activity of gemcitabine in human pancreatic cancer through inhibition of tumor growth, depletion of the antiapoptotic proteins, and induction of apoptosis.

    References: Br J Haematol. 2013 Apr;161(1):117-27; Leukemia. 2014 Jan;28(1):155-65. 

    Related CAS #: 1421923-86-5 (E-isomer)   1621865-82-4 (E-isomer)  1393477-72-9 (free base)                           

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    Molecular Weight (MW)443.31
    FormulaC17H11F6N7O 
    CAS No.1393477-72-9
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 89 mg/mL (200.8 mM)
    Water: <1 mg/mL
    Ethanol: 40 mg/mL (90.2 mM)
    Solubility (In vivo)2% DMSO+49% PEG 300+dd H2O: 5mg/mL 
    Synonyms

    KPT-330; KPT 330; KPT330

    Chemical Name: (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-N'-(pyrazin-2-yl)acrylohydrazide 

    SMILES Code: O=C(NNC1=NC=CN=C1)/C=C\N2N=C(C3=CC(C(F)(F)F)=CC(C(F)(F)F)=C3)N=C2

    Exact Mass: 443.09293 


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    In Vitro

    In vitro activity: As the clinical candidate analog of KPT-185, KPT-330 exhibits similar effects on the viability of T-ALL cells and elicits rapid apoptotic response. KPT-330 also reduces cell growth in MOLT-4, Jurkat, HBP-ALL, KOPTK-1, SKW-3, and DND-41 cell lines, with IC50 values of 34-203 nM.


    Cell Assay: Cell lines are cultured in RPMI 1640 medium, supplemented with 10% fetal bovine serum and penicillin/streptomycin. Cell Titer Glo assay is used to assess cell viability upon treatment with either dimethyl sulfoxide (DMSO) or KPT-330. Cells are plated at a density of 10 000 cells per well in a 96-well plate and incubated with DMSO or increasing concentrations of KPT-330. The cell viability is measured after 72 h exposure to KPT-330 and reported as a percentage of DMSO control cells. Jurkat cells that overexpress BCL2 are generated using MSCV-IRES-GFP retroviral expression system. Jurkat cells infected with BCL2 or control vector viruses are sorted by flow cytometry and the expression of BCL2 confirmed by Western blot analysis using BCL2 antibody.

    In VivoKPT-330 dramatically suppresses the growth of T-ALL cells (MOLT-4) and AML cells (MV4–11) in vivo, with little toxicity to normal haematopoietic cells. In SCID mice with diffuse human MM bone lesions, KPT-330 inhibits MM-induced bone lysis and prolongs survival. Moreover, KPT-330 directly impairs osteoclastogenesis and bone resorption by blocking RANKL-induced NF-κB and NFATc1, with minimal impact on osteoblasts and BMSCs.
    Animal modelT-ALL and AML orthograft mouse model
    Formulation & Dosage Formulated in Pluronic F-68/PVP-K29/32; 20 -25 mg/kg; oral gavage
    References

    Br J Haematol. 2013 Apr;161(1):117-27; Leukemia. 2014 Jan;28(1):155-65. 


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

    Selinexor (KPT-330)

    KPT-185 induces rapid apoptotic cell death in T-ALL cells. Br J Haematol. 2013 Apr;161(1):117-27.
     

    Selinexor (KPT-330)

    SINE compounds dramatically suppress the growth of MOLT-4 cells engrafted into NSG mice. Br J Haematol. 2013 Apr;161(1):117-27.


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