TY - JOUR
T1 - An antagonist of dishevelled protein-protein interaction suppresses β-catenin-dependent tumor cell growth
AU - Fujii, Naoaki
AU - You, Liang
AU - Xu, Zhidong
AU - Uematsu, Kazutsugu
AU - Shan, Jufang
AU - He, Biao
AU - Mikami, Iwao
AU - Edmondson, Lillian R.
AU - Neale, Geoffrey
AU - Zheng, Jie
AU - Guy, R. Kiplin
AU - Jablons, David M.
PY - 2007/1/15
Y1 - 2007/1/15
N2 - Recent progress in the development of inhibitors of protein-protein interactions has opened the door for developing drugs that act by novel and selective mechanisms. Building on that work, we designed a small-molecule inhibitor of the Wnt signaling pathway, which is aberrantly activated across a wide range of human tumors. The compound, named FJ9, disrupts the interaction between the Frizzed-7 Wnt receptor and the PDZ domain of Dishevelled, down-regulating canonical Wnt signaling and suppressing tumor cell growth. The antitumorigenic effects of FJ9 were pronounced, including induction of apoptosis in human cancer cell lines and tumor growth inhibition in a mouse xenograft model. FJ9 is thus among the first non-peptide inhibitors to show therapeutic efficacy through disruption of PDZ protein-protein interactions.
AB - Recent progress in the development of inhibitors of protein-protein interactions has opened the door for developing drugs that act by novel and selective mechanisms. Building on that work, we designed a small-molecule inhibitor of the Wnt signaling pathway, which is aberrantly activated across a wide range of human tumors. The compound, named FJ9, disrupts the interaction between the Frizzed-7 Wnt receptor and the PDZ domain of Dishevelled, down-regulating canonical Wnt signaling and suppressing tumor cell growth. The antitumorigenic effects of FJ9 were pronounced, including induction of apoptosis in human cancer cell lines and tumor growth inhibition in a mouse xenograft model. FJ9 is thus among the first non-peptide inhibitors to show therapeutic efficacy through disruption of PDZ protein-protein interactions.
UR - http://www.scopus.com/inward/record.url?scp=33846673934&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846673934&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-06-2726
DO - 10.1158/0008-5472.CAN-06-2726
M3 - Article
C2 - 17234765
AN - SCOPUS:33846673934
SN - 0008-5472
VL - 67
SP - 573
EP - 579
JO - Cancer Research
JF - Cancer Research
IS - 2
ER -
