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. 2009 Nov 23;10(17):2721-4.
doi: 10.1002/cbic.200900552.

Discovery of a small-molecule inhibitor of the KIX-KID interaction

Bingbing X Li  1 , Xiangshu Xiao
Affiliations

Discovery of a small-molecule inhibitor of the KIX-KID interaction

Bingbing X Li et al. Chembiochem. .
No abstract available

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Figures

Figure 1
Figure 1
Design principle of and fusion constructs for the KIX–KID Renilla luciferase complementation assay. NLS : nuclear localization sequence.
Figure 2
Figure 2
Compound 1 inhibits KIX–KID interaction in living cells. A) Forskolin dose-dependently stimulates KIX–KID interaction in cells. HEK293T cells were transfected with RLucC–KIX and KID–RLucN. The transfected cells were then treated with increasing concentrations of forskolin for 2 h. The Renilla luciferase activity was then measured by adding coelenterazine to the cells. B) Compound 1 inhibits KIX–KID interaction in cells. Same as in (A), except that the transfected cells were pretreated with increasing concentrations of 1 (▲) or 3 (●) before the addition of forskolin (2.5 μm).
Figure 3
Figure 3
Compound 1 inhibits the KIX–KID interaction in vitro. A) Renilla luciferase activity was specifically reconstituted upon mixing RLucC–KIX and KID–RLucN. B) Compound 1 inhibits the KIX–KID interaction in vitro. RLucC–KIX and KID–RLucN were combined in the presence of varying concentrations of 1 (●), 2 (■) or 3 (▲). The mixture was then incubated on ice for 24 h, and the remaining luciferase activity was measured.
Figure 4
Figure 4
Compound 1 binds KIX and inhibits CREB-mediated gene transcription. A) Compound 1 binds His6KIX. Different concentrations of His6KIX were immobilized on Ni–Sepharose beads and incubated with either 1 (□) or 2 (■; 50 μm). The fraction of unbound compounds was analyzed by HPLC. B) Compound 1 inhibits CREB-mediated gene transcription in HEK293T cells. CRE-RLuc-transfected HEK293T cells were treated with increasing concentrations of 1 (□) or 2 (■). The Renilla luciferase activity was measured 4.5 h after forskolin stimulation.
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