Hedgehog pathway inhibitors
Oral Smoothened blockers for advanced basal cell carcinoma and, with low-dose cytarabine, for AML. All cause severe birth defects.
What they are
Vismodegib and sonidegib treat basal cell carcinoma that surgery or radiation cannot handle; glasdegib treats newly diagnosed AML in older or unfit adults together with low-dose cytarabine (suffix «-degib»).
Mechanism of action
The Hedgehog pathway shapes the embryo. Its receptor PTCH1 normally restrains Smoothened (SMO); when PTCH1 is lost, as in most basal cell carcinomas, SMO drives GLI transcription factors continuously. These drugs bind SMO and switch the pathway off. Because Hedgehog signalling patterns the face, brain and limbs, blocking it in pregnancy causes severe malformations or fetal death.
Target: Smoothened (SMO), a seven-transmembrane receptor of the Hedgehog pathway
Drugs in this class
- VismodegibThe first oral Hedgehog pathway inhibitor: blocks Smoothened in advanced basal cell carcinoma. Causes severe birth…Smoothened (SMO) receptor
- SonidegibAn oral Smoothened blocker for locally advanced basal cell carcinoma, taken on an empty stomach. Muscle damage and…Smoothened (SMO) receptor
- GlasdegibAn oral Smoothened blocker used with low-dose cytarabine for newly diagnosed AML in older or unfit adults. Watch the…Smoothened (SMO) receptor
Test yourself
Think of the answer, then tap the question to see it.
Which protein do Hedgehog pathway inhibitors block?
Smoothened (SMO).
Why are these drugs teratogenic?
Hedgehog signalling patterns the embryo (face, brain, limbs); blocking it causes malformations.
Which member is used for leukaemia?
Glasdegib, with low-dose cytarabine in AML.
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); Vismodegib: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2016); Glasdegib: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2019); RCSB PDB - 5L7I: Structure of human Smoothened in complex with Vismodegib (RCSB Protein Data Bank, 2026).
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Representative model, for educational purposes only.