Related Experiment Video
Updated: Jun 20, 2026

Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
Published on: January 31, 2025
GDC-0449-a potent inhibitor of the hedgehog pathway
Kirk D Robarge1, Shirley A Brunton, Georgette M Castanedo
1Genentech, Small Molecule Drug Discovery 1 DNA Way, South San Francisco, CA 94080, United States. kir@gene.com
Abstract:
SAR for a wide variety of heterocyclic replacements for a benzimidazole led to the discovery of functionalized 2-pyridyl amides as novel inhibitors of the hedgehog pathway. The 2-pyridyl amides were optimized for potency, PK, and drug-like properties by modifications to the amide portion of the molecule resulting in 31 (GDC-0449). Amide 31 produced complete tumor regression at doses as low as 12.5mg/kg BID in a medulloblastoma allograft mouse model that is wholly dependent on the Hh pathway for growth and is currently in human clinical trials, where it is initially being evaluated for the treatment of BCC.
Related Concept Videos
Hedgehog Signaling Pathway
Hedgehog Signaling Pathway
Inhibition of CDK Activity
Inhibition of Cdk Activity
Role Of Notch Signalling In Intestinal Stem Cell Renewal
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
The JAK-STAT Signaling Pathway

