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ID: ALA1149081

Journal: Bioorg Med Chem Lett

Title: Identification and structure-activity relationships of ortho-biphenyl carboxamides as potent Smoothened antagonists inhibiting the Hedgehog signaling pathway.

Authors: Peukert S, Jain RK, Geisser A, Sun Y, Zhang R, Bourret A, Carlson A, Dasilva J, Ramamurthy A, Kelleher JF.

Abstract: Ortho-biphenyl carboxamides, originally prepared as inhibitors of microsomal triglyceride transfer protein (MTP) have been identified as novel inhibitors of the Hedgehog signaling pathway. Structure-activity relationship studies for this class of compounds reduced MTP inhibitory activity and led to low nanomolar Hedgehog inhibitors. Binding assays revealed that the compounds act as antagonists of Smoothened and show cross-reactivity for both the human and mouse receptor.

CiteXplore: 19091559

DOI: 10.1016/j.bmcl.2008.11.096