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Biomap#60

Title: List of Hedgehog pathway inhibitors
 
Legend: The Hedgehog pathway is a major regulator for cell differentiation, tissue polarity, and cell proliferation. It has also been involved in tumor (including melanoma [4]) development and progression due to its role in cell stemness and angiogenesis. Briefly, Hedgehog ligands (Sonic, Desert, Indian) bind to and inhibit the Hedgehog receptor Patched-1 (PTCH1), which then cannot inhibit Smootened (SMO); SMO can thus activate glioma associated oncogene (GLI), which in turn transactivates Hedgehog target genes. Hedgehog inhibitors are being evaluated as anticancer agents (e.g.: anti-SHH antibody, CUR61414, Cyclopamine, Gant-58, Gant-61, GDC-0449, GLI antisense, HhAntag-691, KAAD-cyclopamine, Jervine, Sant-1, Sant-2, Vitamin D3). REFERENCES: [1] Xie J, Curr Oncol Rep 2008, 10:107-13. [2] Rubin LL et al, Nat Rev Drug Discov 2006, 5:1026-33. [3] Lauth M et al, Curr Opin Investig Drugs 2007, 8:457-61. [4] Stecca B et al, Proc Natl Acad Sci USA 2007, 104:5895-900
Author: The MMMP Team (updated: May 2008)

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