1-amino-4-benzylphthalazines as orally bioavailable smoothened antagonists with antitumor activity

K Miller-Moslin, S Peukert, RK Jain…

Index: Miller-Moslin, Karen; Peukert, Stefan; Jain, Rishi K.; McEwan, Michael A.; Karki, Rajesh; Llamas, Luis; Yusuff, Naeem; He, Feng; Li, Yanhong; Sun, Yingchuan; Dai, Miao; Perez, Lawrence; Michael, Walter; Sheng, Tao; Lei, Huangshu; Zhang, Rui; Williams, Juliet; Bourret, Aaron; Ramamurthy, Arun; Yuan, Jing; Guo, Ribo; Matsumoto, Melissa; Vattay, Anthony; Maniara, Wieslawa; Amaral, Adam; Dorsch, Marion; Kelleher III, Joseph F. Journal of Medicinal Chemistry, 2009 , vol. 52, # 13 p. 3954 - 3968

Full Text: HTML

Citation Number: 79

Abstract

Abnormal activation of the Hedgehog (Hh) signaling pathway has been linked to several types of human cancers, and the development of small-molecule inhibitors of this pathway represents a promising route toward novel anticancer therapeutics. A cell-based screen performed in our laboratories identified a new class of Hh pathway inhibitors, 1-amino-4- benzylphthalazines, that act via antagonism of the Smoothened receptor. A variety of ...