1. Academic Validation
  2. Identification and structure-activity relationships of ortho-biphenyl carboxamides as potent Smoothened antagonists inhibiting the Hedgehog signaling pathway

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

  • Bioorg Med Chem Lett. 2009 Jan 15;19(2):328-31. doi: 10.1016/j.bmcl.2008.11.096.
Stefan Peukert 1 Rishi K Jain Adrian Geisser Yingchuan Sun Rui Zhang Aaron Bourret Adam Carlson Jennifer Dasilva Arun Ramamurthy Joseph F Kelleher
Affiliations

Affiliation

  • 1 Novartis Institutes for BioMedical Research, Inc., 250 Massachusetts Avenue, Cambridge, MA 02139, USA. stefan.peukert@novartis.com
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.

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