Home GPCR & G Protein Hedgehog/Smoothened

Hedgehog/Smoothened inhibitors

Smoothened (smo), a G protein-coupled receptor, drives the Hedgehog signalling pathway and is involved in gene expression and Gli family transcription factors. The core members of the Smo signalling pathway include the ligand (Hedgehog, Hh), the receptor (Patched, Ptc), several transducers such as Smoothened (Smo) and the ytoplasmic complex formed by the kinesin-like protein Costal-2 (Cos2), the serine/threonine kinase Fused (Fu), the novel protein Suppressor of fused [Su(fu)], and the transcription factor Cubitus interruptus (Ci). SMO is classified as a proto-oncogene because the tumour suppressor PTCH represses signalling by SMO, and SHH relieves this repression.

Other GPCR & G Protein Related Inhibitors

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Isoform-selective Products

Cat.No. Product Name Information Product Use Citations Product Validations
S1082 Vismodegib (GDC-0449) Vismodegib (GDC-0449) is a potent, novel and specific hedgehog inhibitor with IC50 of 3 nM and also inhibits P-gp with IC50 of 3.0 μM in a cell-free assay.
Nat Commun, 2025, 16(1):5137
Nat Commun, 2025, 16(1):1092
Nat Commun, 2025, 16(1):1267
Verified customer review of Vismodegib (GDC-0449)
S1146 Cyclopamine (11-Deoxojervine) Cyclopamine (11-deoxojervine) is a specific Hedgehog (Hh) signaling pathway antagonist of Smoothened (Smo) with IC50 of 46 nM in TM3Hh12 cells.
Nat Commun, 2025, 16(1):1267
EMBO Mol Med, 2025, 17(2):336-364
Development, 2025, 152(8)dev204324
Verified customer review of Cyclopamine (11-Deoxojervine)
S7779 SAG (Smoothened Agonist) Hydrochloride SAG (Smoothened Agonist) HCl is a cell-permeable Smoothened (Smo) agonist with EC50 of 3 nM in Shh-LIGHT2 cells.
Nat Commun, 2025, 16(1):6545
Nat Commun, 2025, 16(1):1267
Theranostics, 2025, 15(14):7127-7153
Verified customer review of SAG (Smoothened Agonist) Hydrochloride
S3042 Purmorphamine Purmorphamine (Shh Signaling Antagonist VI), which directly binds and activates Smoothened, blocks BODIPY-cyclopamine binding to Smo with IC50 of ~ 1.5 μM in HEK293T cell and also is an inducer of osteoblast differentiation with EC50 of 1 μM. Purmorphamine can reduce both basal and induced autophagy.
Nat Commun, 2025, 16(1):8693
Commun Biol, 2025, 8(1):1177
Development, 2025, 152(3)DEV204214
Verified customer review of Purmorphamine
S8075 GANT61 GANT61 (NSC 136476) is an inhibitor for GLI1 as well as GLI2-induced transcription, inhibits hedgehog with IC50 of 5 μM in GLI1 expressing HEK293T cell, displays selectivity over other pathways, such as TNF and glucocorticoid receptor gene transactivation. This compound induces apoptosis and activates protective autophagy in LX-2 cells.
Nat Commun, 2025, 16(1):1267
Theranostics, 2025, 15(18):9819-9837
J Exp Clin Cancer Res, 2025, 44(1):22
Verified customer review of GANT61
S2151 Sonidegib Sonidegib is a Smoothened (Smo) antagonist, inhibiting Hedgehog (Hh) signaling with IC50 of 1.3 nM (mouse) and 2.5 nM (human) in cell-free assays, respectively. Phase 3.
Nat Commun, 2025, 16(1):5137
Nat Commun, 2025, 16(1):1267
Method Protocol, 2025, 8(3)59
Verified customer review of Sonidegib
S2476 Itraconazole Itraconazole is a relatively potent inhibitor of CYP3A4 with IC50 of 6.1 nM, used as a triazole antifungal agent. This compound is a potent antagonist of the Hedgehog (Hh) signaling pathway. It also suppresses the growth of glioblastoma through induction of autophagy.
Cell Rep Med, 2025, S2666-3791(25)00272-1
Infect Drug Resist, 2025, 18:783-789
Toxicol Appl Pharmacol, 2025, 502:117404
Verified customer review of Itraconazole
S7092 SANT-1 SANT-1 directly binds to Smoothened (Smo) receptor with Kd of 1.2 nM and inhibits Smo agonist effects with IC50 of 20 nM.
Nat Commun, 2024, 15(1):9771
Stem Cell Reports, 2024, 19(7):973-992
Front Immunol, 2023, 14:1258074
Verified customer review of SANT-1
S6384 SAG SAG (Smoothened Agonist) is a potent agonist of Smoothened (Smo). This compound induces firefly luciferase expression in Shh-LIGHT2 cells with an EC50 of 3 nM.
Cell Rep, 2025, 44(5):115597
Open Biol, 2025, 15(4):240342
Neural Plast, 2025, 2025:9933756
S7138 BMS-833923 BMS-833923 (XL139) is an orally bioavailable Smoothened antagonist. Phase 2.
Nat Commun, 2025, 16(1):4983
Sci Rep, 2022, 12(1):7
Mol Cancer Res, 2021, molcanres.MCR-21-0257-A.2021
Verified customer review of BMS-833923

Signaling Pathway Map