Hedgehog/Smoothened

Triparanol (NSC-65345) interferes with posttranslational modification of Hedgehog signaling molecules as well as the sterol sensing domain of its receptor PTCH1, leading to down-regulation of Hedgehog signaling. Triparanol suppresses human tumor growth and is an antilipemic agent with high ophthalmic toxicity.

Purmorphamine (Shh Signaling Antagonist VI), which directly binds and activates Smoothened, blocks BODIPY-cyclopamine binding to Smo. It also is an inducer of osteoblast differentiation.

SAG (Smoothened Agonist) is a Smo receptor agonist (EC50=3 nM) that is cell-permeable and selective. SAG regulates Smo activity by binding directly to the Smo helix and can activate the Hedgehog signaling pathway.

GANT 61 (GANT61) is an inhibitor for Gli1 and Gli2.

Vismodegib (GDC-0449) is a hedgehog pathway inhibitor (IC50: 3 nM). It also inhibits P-gp (IC50: 3.0 μM), ABCG2 (IC50: 1.4 μM).

Sonidegib (Erismodegib), a Smoothened (Smo) antagonist, inhibits Hedgehog (Hh) signaling with IC50 of 1.3 nM (mouse) and 2.5 nM (human), respectively.

Cyclopamine (11-Deoxojervine), a Smoothened (Smo) antagonist (IC50: 46 nM in TM3Hh12 cells), belongs to the group of steroidal jerveratrum alkaloids.

RU-SKI 43 is a potent and selective hedgehog acyltransferase (Hhat) inhibitor with an IC50 of 850 nM. It exhibits anticancer activity and is a potential treatment for lung adenocarcinomas. RU-SKI 43 reduces Gli-1 activation through smoothening-independent non-canonical signaling and inhibits Akt and mTOR pathway activity.

Ellagic acid (Gallogen), a thickened tetracyclic natural product, is a potent CK2 inhibitor (IC50=40 nM; Ki=20 nM) with ATP-competitive properties. Ellagic acid is an antioxidant and also possesses antiproliferative activity.

The biological activity of Jervine (Jerwiny) is mediated via its interaction with the 7 passes transmembrane protein Smoothened. Jervine binds with and inhibits smoothened, which is an integral part of the Hedgehog signaling pathways. With smoothened inhibited, the GLI1 transcription cannot be activated and Hedgehog target genes cannot be transcribed.

TAK-441 is an orally active inhibitor of Hedgehog signaling(IC50 = 4.4 nM) with potent antitumor activity. TAK-441 suppresses transcription factor Gli1 mRNA expression and tumor growth.

Itraconazole (R51211) is a triazole antifungal agent that inhibits cytochrome P-450-dependent enzymes necessary for ERGOSTEROL synthesis.

SAG dihydrochloride, a powerful agonist of the Smoothened (Smo) receptor (EC 50 = 3 nM; Kd = 59 nM), effectively activates the Hedgehog signaling pathway. It also negates the effects of Cyclopamine inhibition on Smo.

SANT-1 directly binds to Smoothened (Smo) receptor (Kd: 1.2 nM) and inhibits Smo agonist effects (IC50: 20 nM).

Ciliobrevin D is a AAA+ ATPase motor cytoplasmic dynein inhibitor. Ciliobrevin D inhibits Hedgehog (Hh) signaling and primary cilia formation and it also inhibits dynein-dependent microtubule gliding and ATPase activity in vitro.

Glasdegib (PF-04449913) (PF-04449913) is a potent, and orally bioavailable Smoothened (Smo) inhibitor with IC50 of 5 nM. Phase 2.

SAG hydrochloride (912545-86-9(free base)) (Smoothened Agonist HCl) acts as an SMO agonist.

Smoothened (Smo) receptor agonist

Hh-Ag1.5 (SAG-1.5) is a potent Hedgehog (Hh) agonist (EC50: 1 nM) and Smoothened (Smo) receptor agonist, with an EC50 of 1 nM and Ki values between 0.5 and 2.3 nM for Smo. Hh-Ag1.5-mediated reprogramming breaks the quiescent state of non-injured hepatic stem cells and thus rescues liver failure. Hh-Ag1.5 induced differentiation of hiPSCs into skin precursor cells, spinal motor neurons and spinal sensory neurons.

Taladegib (LY2940680) is an orally bioavailable small molecule antagonist of the Hedgehog (Hh)-ligand cell surface receptor smoothened (Smo) with potential antineoplastic activity.

BMS-833923 (XL-139), an orally bioavailable Smoothened antagonist, inhibits BODIPY cyclopamine binding to SMO in a dose-dependent manner (IC50: 21 nM).

ALLO-2 is a Inhibitor of Drug-Resistant Smo Mutant.It inhibits Smo agonist Hh-Ag1.5-induced luciferase expression in TM3-Gli-Luc cells with IC50 of 6 nM.

SAG 21k is an orally bioactive and potent Hedgehog signaling activator that crosses the blood-brain barrier for the study of cartilage regeneration.

Ciliobrevin A (HPI-4) is an inhibitor of the hedgehog signaling pathway with an IC50 of less than 10 μM.