320418-04-0Relevant articles and documents
1-Amino-4-benzylphthalazines as orally bioavailable smoothened antagonists with antitumor activity
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.
experimental part, p. 3954 - 3968 (2010/01/16)
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 analogues were synthesized and their structure-activity relationships determined. This optimization resulted in the discovery of high affinity Smoothened antagonists, one of which was further profiled in vivo. This compound displayed a good pharmacokinetic profile and also afforded tumor regression in a genetic mouse model of medulloblastoma.
ORGANIC COMPOUNDS AND THEIR USES
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Page/Page column 41; 45, (2008/12/07)
The present disclosure relates to compounds relating to the diagnosis and treatment of pathologies relating to the Hedgehog pathway, including but not limited to tumor formation, cancer, neoplasia, and non-malignant hyperproliferative disorders; specifically relating to compounds of formula (I).
