KPT276 (KPT 276) is an orally bioavailable selective inhibitor of nuclear export (SINE) that irreversibly bind to CRM1 and block the function of CRM1.

KPT-276 在MCL细胞中显著抑制生长并诱导凋亡。[2] KPT-276 特异性并不可逆地抑制XPO1的核输出功能，降低了12种HMCLs的存活率。KPT-276 亦在原发性MM患者样本中积极诱导凋亡。[3]

KPT-276在几种小鼠模型中显示出显著的抗癌活性。在异种移植AML（急性髓性白血病）小鼠模型中，KPT-276显著延长患病小鼠的生存时间并减少白血病负担。[1] 在携带MCL（套细胞淋巴瘤）的严重联合免疫缺陷小鼠模型中，KPT-276显著抑制肿瘤生长，而且没有引起严重的毒性效应。[2] 在Vk*MYC易位的MM（多发性骨髓瘤）转基因小鼠模型中，KPT-276能减少单克隆峰值，并在异种移植MM小鼠模型中抑制肿瘤生长。[3]

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.