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Gli proteins are the effectors of Hedgehog (Hh) signaling and have been shown to be involved in cell fate determination, proliferation and patterning in many cell types and most organs during embryo development. The Gli transcription factors activate/inhibit transcription by binding to Gli responsive genes and by interacting with the transcription complex. The Gli transcription factors have DNA binding zinc finger domains which bind to consensus sequences on their target genes to initiate or suppress transcription. Research showed that mutating the Gli zinc finger domain inhibited the proteins effect proving its role as a transcription factor. Gli proteins have an 18-amino acid region highly similar to the α-helical herpes simplex viral protein 16 activation domain.

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GANT 58 (NSC 75503) is a potent Gli antagonist and Hedgehog signaling (Hh) inhibitor that inhibits GLI1-induced transcription with IC50 of 5 uM; efficiently inhibits in vitro tumor cell proliferation in a GLI-dependent manner and successfully blocks cell growth in an in vivo xenograft model of human prostate cancer cells harboring downstream activation of the Hh pathway.




JK184 is an ntagonist of the hedgehog (Hh) signaling pathway and Gli inhibitor; inhibits GLI1 mRNA expression and decreases the number of colonies formed in TN-IBC (SUM149) and TNBC (MDA-MB-231 and SUM159) cell lines; significantly down-regulates GLI1 targets that regulate cell cycle (cyclin D and E) and apoptosis (Bcl2); JK184 is a potent inhibitor of microtubule assembly and that microtubule-depolymerizing agents can either negatively or positively regulate the Gli family of transcription factors, dependending on the mechanism by which the pathway is activated.




Hedgehog-IN-7d is a potent, cell-permeable Hedgehog (Hh) pathway inhibitor that inhibits Gli transcription activity with an IC50 value of 70 nM.




FN1-8 (Gli inhibitor FN1-8) is a novel, synthetic small molecule that efficiently interferes with Gli/TAF9 interaction and downregulate Gli/TAF9-dependent transcriptional activity (at 15 uM); inhibits non-canonical Gli activation and acts downstream of the canonical Hh pathway; suppresses cancer cell proliferation in vitro and inhibits tumor growth in vivo.


Glabrescione B


Glabrescione B (GlaB) is a small molecule binding to Gli1 zinc finger and impairing Gli1 activity by interfering with Gli1/DNA interaction, inhibits Hh signaling by impairing Gli1 function; inhibits the growth of Hedgehog-dependent tumor cells in vitro and in vivo, inhibits Gli1-dependent growth of cerebellum-derived normal progenitors; inhibits the growth of Gli-dependent medulloblastoma and tumor-derived stem-like cells; inhibits the growth of Gli-dependent basal cell carcinoma in vitro and in vivo.

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