nsc228155 is a potent inhibitor of kix-kid interaction.cyclic-amp response-element binding protein (creb) is identified as a stimulus-activated transcription factor. its transcription activity needs its binding with creb-binding protein (cbp) after creb is phosphorylated at ser133. the domains involved for creb-cbp interaction are kinase-inducible domain (kid) from creb and kid-interacting domain (kix) from cbp.
previous study found that nsc228155 could dose-dependently inhibit kix–kid interaction as measured by the split rluc assay. in living hek 293t cells, nsc228155 could inhibit creb-mediated gene transcription with an ic50 of 2.09 μm. nsc228155 also inhibited vp16-creb-mediated gene transcription with an ic50 of 6.14 μm. though this was around 3-fold higher than the ic50 of creb-mediated gene transcription, such results indicated that nsc228155 was not particularly selective in inhibiting kix–kid interaction inside these living cells. therefore, although nsc228155 was a potent inhibitor of kix-kid interaction, it was not selective against creb-mediated gene transcription, and further sar studies identified a 4-aniline substituted analog displaying a higher selectivity index [1].
| EGFR | KIX-KID 0.36 μM (IC 50 ) |
0.36 μm for kix-kid interaction
[1] xie f, li bx, broussard c, xiao x. identification, synthesis and evaluation of substituted benzofurazans as inhibitors of creb-mediated gene transcription. bioorg med chem lett. 2013 oct 1;23(19):5371-5.
