IndraLab

Statements

Pevonedistat inhibits NFKBIA. 6 / 6
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eidos
"However , contrary to TNF-alpha , MLN4924 did not induce IkappaB-alpha degradation in treated cells ."
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"MLN4924 Dysregulates Subcellular Localization of Phospho-NFkappaB and p65 and Phospho-IkappaB-alpha."
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"These included pevonedistat ( MLN4924 ) , a NEDD8-activating enzyme ( NAE ) inhibitor , which blocks NFkappaB activation by preventing the NEDDylation and consequent degradation of IkappaBalpha.44 ,45 Also tested were the MEK inhibitor trametinib ,46 the p38 MAPK inhibitor VX-745 ,47 and JNK inhibitor 8 ( JNKi8 ) .48,49 In JAK2 mutant HEL cells , pevonedistat was shown to inhibit degradation of IkappaBalpha ( Figure 7a ) , without affecting levels of p-p65 / RELA or pSTAT3 / 5 ( Figure 7a , b ) ."
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"Pevonedistat blocks degradation of IkappaBalpha , resulting in inhibition of NF-kB , upon which LSCs are dependent for survival [ 99 ] ."
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"Given that 1) matrix metalloproteinase 9 (MMP-9) promotes cell migration XREF_BIBR, 2) MMP-9 is a known target of NFkappaB XREF_BIBR and 3) MLN4924 inactivates NFkappaB by causing accumulation of IkappaBalpha (XREF_FIG), we determined potential involvement of MMP-9 in cell migration and found that MLN4924 effectively inhibited expression of MMP-9mRNA in both gastric cancer cell lines (XREF_FIG)."
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"However, contrary to TNF-alpha, MLN4924 did not induce IkappaB-alpha degradation in treated cells."
33572115