product name KPT-276
Description: 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.
426.26
Formula
C16H10F8N4O
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
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19409231
| 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. Kinase Assay: 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 model | Human leukemia (MV4-11) xenografts are established in mice. |
| Formulation & Dosage | Dissolved 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. |
