| Name | KPT276 |
| Description | KPT276 (KPT 276) is an orally bioavailable selective inhibitor of nuclear export (SINE) that irreversibly bind to CRM1 and block the function of CRM1. |
| Kinase Assay | Kinase inhibition assay: A glutathione S-transferase-tagged kinase domain construct of the intracellular portion of the PDGFR-β (amino acids 693-1401, accession no. J03278) is expressed in Sf-9 cells (baculovirus expression system). Enzyme kinetics are determined by incubating the enzyme with increasing concentrations of ATP in phosphorylation buffer [50 mmol/L HEPES (pH 7.3), 125 mmol/L NaCl, 24 mmol/L MgCl2 in Nunc Immuno MaxiSorp 96-well plates previously coated with 100 μL of 100 μg/mL poly-Glu-Tyr (4:1 ratio) diluted in PBS. After 10 minutes, the plates are washed (PBS, 0.1% Tween 20), incubated with anti-phosphotyrosine-horseradish peroxidase antibody, and diluted in PBS, 0.05% Tween 20, 3% BSA for 30 minutes at room temperature. The plates are washed as above and incubated with 3,3',5,5'-tetramethylbenzidine. The reaction is stopped by adding an equal volume of 0.09 NaH2SO4. The phosphotyrosine-dependent signal is then quantitated on a plate reader at 450 nm. For routine enzyme assays, the enzyme is incubated with 10 μM ( final) ATP in the presence of compound diluted in DMSO (1.6% v/v DMSO assay final) for 30 minutes at room temperature in plates, as above, previously coated with 100 μL of 6.25 μg/mL poly-Glu-Tyr. The remainder of the assay is carried out as above, and IC50 values are calculated as percent inhibition of control. |
| In vitro | KPT-276 results in significant growth inhibition and apoptosis induction in MCL cells. [2] 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. [3] |
| In vivo | KPT-276 significantly prolongs survival of leukemic mice and reduces leukemic burden in a xenograft AML mouse model. [1] KPT-276 significantly suppresses tumor growth in an MCL-bearing severe combined immunodeficient mouse model without severe toxicity. [2] KPT-276 reduces monoclonal spikes in the Vk*MYC transgenic MM mouse model, and inhibits tumor growth in a xenograft MM mouse model. [3] |
| Storage | Shipping with blue ice/Shipping at ambient temperature. |
| Solubility Information | H2O : < 1 mg/mL (insoluble or slightly soluble)
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 2 mg/mL (4.69 mM), Sonication is recommended.
DMSO : 11 mg/mL (25.81 mM), Sonication is recommended.
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
|
| Keywords | KPT276 | CRM1 |
| Inhibitors Related | Eltanexor | Selinexor (KPT-330) | PKF050-638 | Leptomycin B | KPT-251 | Leptomycin A | Eltanexor Z-isomer | (E)-KPT330 | Verdinexor | CRM1 degrader 1 | CBS9106 | KPT185 |
| Related Compound Libraries | Bioactive Compound Library | Membrane Protein-targeted Compound Library | Inhibitor Library | NO PAINS Compound Library | Orally Active Compound Library | Bioactive Compounds Library Max | Covalent Inhibitor Library | Fluorochemical Library | Anti-Cancer Compound Library |
United States
