SANT-1 is a cell-permeable Smoothened antagonist that inhibits the Hedgehog pathway. SANT-1 downregulates Hh target gene expressions such as Gli1 and Ptch1 to suppress tumor cell proliferation and reduces Gli-mediated transcription by blocking the Smo downstream pathway. SANT-1 can be used for research on medulloblastoma, basal cell carcinoma, glioma, pancreatic cancer, and non-small cell lung cancer[1-4].
In vitro, treatment of ASZ001 cells with 10μM SANT-1 for 48 hours inhibited hedgehog signaling activity in the cells[5]. Treatment of A172, U87MG, and T98G cells, SVG-p12 cells, and U87MG-derived cells with 10-70μM SANT-1 for 24-48 hours decreased Gli1, Nestin, IQGAP-1, and cyclin D1 expressions, reduced the number and size of glioma stem-like spheres, and lowered proliferation ability[6]. Treatment of ammonium ferric citrate-induced HEI-OC1 cells with 10-20μM SANT-1 for 24 hours protected HEI-OC1 cells from ammonium ferric citrate-induced damage and restored intracellular iron overaccumulation after ammonium ferric citrate treatment[7].
References:[1] Stanton BZ, Peng LF. Small-molecule modulators of the Sonic Hedgehog signaling pathway. Mol Biosyst. 2010 Jan;6(1):44-54.
[2] McGaugh EC, Nostro MC. Efficient Differentiation of Pluripotent Stem Cells to NKX6-1+ Pancreatic Progenitors. J Vis Exp. 2017 Mar 7;(121):55265.
[3] Okolowsky N, Furth PA, Hamel PA. Oestrogen receptor-alpha regulates non-canonical Hedgehog-signalling in the mammary gland. Dev Biol. 2014 Jul 15;391(2):219-29.
[4] Chun SG, Zhou W, Yee NS. Combined targeting of histone deacetylases and hedgehog signaling enhances cytoxicity in pancreatic cancer. Cancer Biol Ther. 2009 Jul;8(14):1328-39.
[5] Dheeraj A, Rigby CM, O'Bryant CL, et al. Silibinin Treatment Inhibits the Growth of Hedgehog Inhibitor Resistant Basal Cell Carcinoma Cells via Targeting EGFR-MAPK-Akt and Hedgehog Signaling. Photochem Photobiol. 2017 Jul;93(4):999-1007.
[6] Dixit D, Ghildiyal R, Anto NP, et al. Guggulsterone sensitizes glioblastoma cells to Sonic hedgehog inhibitor SANT-1 induced apoptosis in a Ras/NFkB dependent manner. Cancer Lett. 2013;336(2):347-358.
[7] Mao H, Li X, Liao Y, et al. Restoring Iron Homeostasis via Smoothened Inhibition: A Novel Strategy Against Hearing Loss. Adv Sci. 2026;13:e20749.