Vismodegib’s mechanism of action

Vismodegib (Vismodegib) inhibits the Hedgehog signaling pathway. The Hedgehog pathway plays a critical role during embryonic development but has limited activity in most adult tissues, except hair, skin and stem cells. In more than 90% of basal cell carcinomas, the Hedgehog signaling pathway is abnormally upregulated. Mutations in key receptor proteins such as Patched (PTCH) and Smoothened (SMO) lead to abnormal transcription of target genes that regulate basal cell growth and proliferation. Vimodegibacts as an SMO antagonist to prevent the activation of GLI1 and GLI2 transcription factors and block the signaling cascade.