Targeting the GLI family of transcription factors for the development of anti-cancer drugs.

Interest in developing inhibitors of GLI1-mediated transcription has significantly increased as its role in multiple oncogenic signaling pathways has been elucidated. To date, it has proven difficult to directly target GLI1 with small molecules, and the majority of compounds that inhibit GLI1 activity function through indirect mechanisms. To date, no direct-acting GLI1 inhibitor has entered clinical trials. The identification and development of new scaffolds that can bind and directly inhibit GLI1 are essential to further advance this class of chemotherapeutics.