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      KPT-276
      KPT-276

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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 #: V1683
      CAS #: 1421919-75-6Purity ≥98%

      Description: This product has been discontinued. KPT-276 is a potent, orally bioavailable, and selective CRM1 inhibitor. KPT-276 rreversibly binds to CRM1 and blocks CRM1-mediated nuclear export. In human multiple myeloma (MM) cell lines (HMCLs), KPT-276 irreversibly and specifically inhibited the nuclear export of XPO1, which encoded CRM1 and significantly reduced the viability of HMCLs. In bone marrow cells isolated from MM patients, KPT-276 induced apoptosis. Also, KPT-276 downregulated the expression of c-MYC, CDC25A and BRD4, which caused G1/S phase arrest.

      References: Blood. 2012 Aug 30;120(9):1765-73; Exp Hematol. 2013 Jan;41(1):67-78.e4. 

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      Molecular Weight (MW)426.26
      FormulaC16H10F8N4O
      CAS No.1421919-75-6
      Storage-20℃ for 3 years in powder form
      -80℃ for 2 years in solvent
      Solubility (In vitro)DMSO: 20 mg/mL (46.9 mM)
      Water: <1 mg/mL
      Ethanol:<1 mg/mL
      Solubility (In vivo)30% PEG400+0.5% Tween80+5% Propylene glycol: 5 mg/mL 
      SynonymsKPT-276; KPT 276; KPT276


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      In Vitro

      In vitro activity: KPT-276 results in significant growth inhibition and apoptosis induction in MCL cells. KPT-276 specifically and irreversibly inhibits the nuclear export function of XPO1, and reduces the viability of 12 HMCLs. KPT-276 also actively induces apoptosis in primary MM patient samples.

      Cell Assay: KPT-276 is an orally bioavailable and selective CRM1 inhibitor that irreversibly binds to CRM1 and blocks CRM1-mediated nuclear export. In human multiple myeloma (MM) cell lines (HMCLs), KPT-276 irreversibly and specifically inhibited the nuclear export of XPO1, which encoded CRM1 and significantly reduced the viability of HMCLs. In bone marrow cells isolated from MM patients, KPT-276 induced apoptosis. Also, KPT-276 downregulated the expression of c-MYC, CDC25A and BRD4, which caused G1/S phase arrest.

      In Vivo KPT-276 significantly prolongs survival of leukemic mice and reduces leukemic burden in a xenograft AML mouse model. KPT-276 significantly suppresses tumor growth in an MCL-bearing severe combined immunodeficient mouse model without severe toxicity. KPT-276 reduces monoclonal spikes in the Vk*MYC transgenic MM mouse model, and inhibits tumor growth in a xenograft MM mouse model.
      Animal modelHuman leukemia (MV4-11) xenografts are established in mice. 
      Formulation & DosageDissolved in DMSO; ~150 mg/kg; Oral administration
      References

      Blood. 2012 Aug 30;120(9):1765-73; Exp Hematol. 2013 Jan;41(1):67-78.e4. 

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

      KPT-276

      CRM1 inhibitor increases survival in a human leukemia xenograft model. Blood. 2012 Aug 30; 120(9): 1765–1773.

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