PF-04449913 (Glasdegib)

Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

Smoothened (SMO) is a protein that plays a vital role in the Hedgehog signaling pathway. It is also known by other names such as SMOH and Smoothened homolog. This protein has a molecular mass of approximately 86 kDa. Smoothened is expressed in a variety of tissues including the brain lungs and kidneys. It functions as a transmembrane protein with seven helices which transmits signals across the cell membrane.

Biological function summary

Smoothened influences cellular processes by participating in the Hedgehog signaling pathway. It operates as part of a complex with the Patched (PTCH) receptor. When the Hedgehog ligand binds to PTCH Smoothened becomes activated. This activation leads to changes in gene expression that control cell growth and differentiation. Smoothened is critical in embryonic development tissue regeneration and stem cell maintenance.

Pathways

Smoothened interacts with essential components of the Hedgehog signaling pathway. This pathway includes proteins like PTCH and Gli transcription factors. Smoothened activation triggers the release of these Gli proteins from inhibitory complexes which then migrate to the nucleus to modulate the transcription of target genes. The Hedgehog pathway is important in regulating developmental processes and cellular responses.

Smoothened has connections to various forms of cancer including basal cell carcinoma and medulloblastoma. Abnormal activation or mutations in Smoothened can lead to unchecked cell proliferation. Smoothened also shows relevance in the development of gliomas. Drugs like 'anti smo' or 'glasdegib' act as Smoothened antagonists aiming to inhibit its function in these diseases by targeting the Hedgehog signaling pathway.