Hedgehog/Smoothened

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).

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.

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

CUR61414 hydrochloride is a potent and cell permeable inhibitor of Hedgehog signaling pathway (IC50 =100-200 nM). CUR61414 hydrochloride is a small-molecule aminoproline class compound. CUR61414 hydrochloride selectively binds to smoothened (Smo, Ki= 44 nM). CUR61414 hydrochloride can induce cancer cells apoptosis without affecting neighboring non-tumor cells.

SMO-IN-2 is a potent smoothened (SMO) inhibitor of hedgehog (Hh) signaling.SMO-IN-2 shows antiproliferative activity and anticancer activity against human medulloblastoma cell lines.SMO-IN-2 can be used in the study of cancer.

CUR61414 is a cell-permeable inhibitor of Hedgehog signaling pathway (IC50 =100-200 nM) and selectively binds to smoothened (Ki = 44 nM).

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

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

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.

HhAntag is a small molecule inhibitor of GLI1-mediated transcription, an essential down-stream element of the Hedgehog (Hh) pathway with the anti-tumor activity.

Ellagic acid (Gallogen) is a fused four ring compound isolated from the kino of Eucalyptus maculata Hook and E. Hemipholia F. Muell. Activates Factor XII of the blood clotting system which also causes kinin release; used in research and as a dye.

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

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.

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

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

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.

MRT-10 is a Smoothened (Smo) receptor antagonist.

MRT-81 is a potent antagonist of human and rodent smoothened receptors that inhibits hedgehog activity with an IC50 value of 41 nM in Shh-light2 cells.It is used in the study of cancer.

AZD8542 is an antagonist of Smoothened (SMO) and a Hedgehog (Hh) pathway antagonist with anticancer and antiproliferative activity that inhibits the growth of tumors in living organisms, and is used in the study of prostate and colon cancer.

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

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.

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

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.

Naftifine Hydrochloride is the hydrochloride salt form of naftifine, an allylamine derivate with synthetic broad-spectrum antifungal activity. Although the exact mechanism through which naftifine hydrochloride exerts its effect is unknown, it appears to selectively inhibit the enzyme squalene 2, 3-epoxidase, thereby inhibiting the biosynthesis of sterol. This results in a decreased amount of sterols, especially ergosterol which is the primary fungal membrane sterol, and a corresponding accumulation of squalene in fungal cells. Naftifine hydrochloride (Naftifine HCl) can be fungicidal as well as fungistatic to yeasts depending on the concentration and the organisms involved.

GANT 58 (NSC-75503) is a potent antagonist of Gli. Which inhibits GLI1-induced transcription (IC50: 5 μM).

MK-4101, an effective inhibitor of the Hedgehog pathway, has anti-tumor activity through the induction of extensive apoptosis and inhibition of proliferation in tumor cells.

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

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.

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

Dynarrestin is an inhibitor of cytoplasmic dyneins 1 and 2. Dynarrestin suppresses hedgehog (Hh)-dependent proliferation of neuronal precursors and tumor cells. It inhibits dynein 1-driven microtubule gliding in vitro plus a range of dynein 1- and 2-depen

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.

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

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.

JK184 is a potent Hedgehog (Hh) pathway inhibitor.

SMANT hydrochloride (N-(4-bromophenyl)-3-(3,5-dimethylpiperidin-1-yl)propanamide hydrochloride) is an antagonist of Smoothened accumulation.

HPI 1 is a hedgehog (Hh) signaling inhibitor. Inhibits Sonic hedgehog (Shh)-, SAG- and Gli-induced Hh pathway activation in Shh-LIGHT2 cells (IC50 values are 1.5, 1.5, 4, and 6 μM for Shh-, SAG-, Gli2- and Gli1-induced activation).

Tolnaftate (NP-27) is a synthetic antifungal agent.

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