Hedgehog/Smoothened
Signaling Pathway Map
Research Area
- Inhibitory Selectivity
- Solubility
| Catalog No. | Product Name | Solubility(25°C) | ||
|---|---|---|---|---|
| Water | DMSO | Alcohol | ||
| S1082 | Vismodegib (GDC-0449) | <1 mg/mL | 84 mg/mL | <1 mg/mL |
| S2157 | Taladegib (LY2940680) | <1 mg/mL | 5 mg/mL | 2 mg/mL |
| S8075 | GANT61 | <1 mg/mL | <1 mg/mL | 12 mg/mL |
| S8200 | MK-4101 | <1 mg/mL | 98 mg/mL | 60 mg/mL |
| S8249 | HPI-4 (Ciliobrevin A) | <1 mg/mL | 71 mg/mL | 1 mg/mL |
| S4747 | Jervine | <1 mg/mL | 5 mg/mL | 2 mg/mL |
| S7160 | Glasdegib (PF-04449913) | <1 mg/mL | 47 mg/mL | <1 mg/mL |
| S1146 | Cyclopamine | <1 mg/mL | <1 mg/mL | 2 mg/mL |
| S2151 | Sonidegib (Erismodegib, NVP-LDE225) | <1 mg/mL | 97 mg/mL | 97 mg/mL |
| S2777 | PF-5274857 | 93 mg/mL | 93 mg/mL | <1 mg/mL |
| S7092 | SANT-1 | <1 mg/mL | 21 mg/mL | 20 mg/mL |
| S7138 | BMS-833923 | <1 mg/mL | 95 mg/mL | <1 mg/mL |
| S3042 | Purmorphamine | <1 mg/mL | 4 mg/mL | <1 mg/mL |
| S8597 | LYN-1604 | 100 mg/mL | 50 mg/mL | 100 mg/mL |
| S7779 | Smoothened Agonist (SAG) HCl | 100 mg/mL | 71 mg/mL | 40 mg/mL |
Isoform-specific Inhibitors
Hedgehog/Smoothened Products
| Catalog No. | 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. |
SMOΔC captured on cholesterol beads in the presence of increasing concentrations of free vismodegib or 20(S)-OHC (h). Results from one of two independent pull-down experiments are shown. |
|
| S2157 |
Taladegib (LY2940680)Taladegib (LY2940680) binds to the Smoothened (Smo) receptor and potently inhibits Hedgehog (Hh) signaling. Phase 1/2. |
||
| S8075 |
GANT61GANT61 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. |
Apoptosis evaluation of UACC62R, SK-MEL-28 R and R3 cells treated with Gant61 (10 μM) for 48 h by flow cytometry detection of Annexin V staining. |
|
| S8200 |
MK-4101MK-4101, a potent inhibitor of the Hedgehog pathway, shows anti-tumor activity through the inhibition of proliferation and induction of extensive apoptosis in tumor cells. |
||
| S8249 |
HPI-4 (Ciliobrevin A)HPI-4 (Ciliobrevin A) is a hedgehog (Hh) pathway antagonist. It blocks Sonic hedgehog (Shh)-induced Hh pathway activation (IC50 = 7 μM) downstream of Smo. |
||
| S4747 |
JervineJervine is a Hedgehog signaling (IC50=500-700 nM) inhibitor that inhibits the sonic hedgehog (shh) pathway by interacting with smoothened. |
||
| S7160 |
Glasdegib (PF-04449913)Glasdegib (PF-04449913) is a potent, and orally bioavailable Smoothened (Smo) inhibitor with IC50 of 5 nM. Phase 2. |
||
| S1146 |
CyclopamineCyclopamine is a specific Hedgehog (Hh) signaling pathway antagonist of Smoothened (Smo) with IC50 of 46 nM in TM3Hh12 cells. |
(A)[3H]thymidine incorporation assay of B16F10 melanoma cells treated with DMSO or cyclopamine after incubation with SA-CM from WT and Cav1KO dermal fibroblasts. Representative phase-contrast images of B16F10 cells treated with SA-CM from WT and Cav1KO fibroblasts with cyclopamine are shown on the right. Similar experiments (B) were done with A-375 cells incubated with SA-CM from hTBJ1-shCtrl and hTBJ1-shCAV1 cells. |
|
| S2151 |
Sonidegib (Erismodegib, NVP-LDE225)Sonidegib (Erismodegib, NVP-LDE225) 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. |
RU-SKI 43 blocks Shh signaling. (a) RU-SKI 43 blocks Gli activation. NIH 3T3 cells were cotransfected with vectors encoding 8× Gli-binding site (GliBS)-Firefly luciferase (unless indicated otherwise), Renilla luciferase reporter (pRL-TK) and Shh. Confluent cells were treated with DMSO, 10 μM LDE225, 10 μM RU-SKI 43 or 10 μM C-2. The firefly luciferase (FL)/Renilla luciferase (RL) ratio in cell lysates was calculated and normalized to that measured in DMSO-treated samples; error bars represent mean ± s.d. (n = 2–3). |
|
| S2777 |
PF-5274857PF-5274857 is a potent and selective Smoothened (Smo) antagonist, inhibits Hedgehog (Hh) signaling with IC50 and Ki of 5.8 nM and 4.6 nM, respectively, and can penetrate the blood–brain barrier. |
||
| S7092 |
SANT-1SANT-1 directly binds to Smoothened (Smo) receptor with Kd of 1.2 nM and inhibits Smo agonist effects with IC50 of 20 nM. |
(D) Percentage cell death of OCI-AML3 cells was measured using the CellTiter-Glo® viability assay following 24 hours treatment with either sequential treatment of 1 μM Vorinostat with low (0.1 μM) or high dose (2.5 μM) SANT-1, or single agents. Data represents a biological replicate of 3, with data presented relative to the DMSO control (0% cell death). (E) Protein expression of SHH was measured following 24 hours treated with the four treatment strategies in OCI-AML3 cells. Equal loading was confirmed with β-Actin |
|
| S7138 |
BMS-833923BMS-833923 is an orally bioavailable Smoothened antagonist. Phase 2. |
Cell viability assays performed on H1650 and H1975 cells with various concentrations of BMS-833923 (B).
|
|
| S3042 |
PurmorphaminePurmorphamine, 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. |
a-d) LoVo cells were separately or simultaneously treated with 1 μM purmorphamine and 1 μM thiostrepton for the indicated time. a The Gli1, FoxM1, and CCNB1 protein expression levels were examined by immunoblotting after drug treatment for 48 h. b Cell viability was detected after 6 days using an MTT assay. c LoVo cells treated with indicated drugs were cultured for 2 weeks, and outgrowth colonies were stained with crystal violet. d The matched colony count of (c). Error bars represent the mean and S.D. of three independent experiments. **, p < 0.01.
|
|
| S8597 |
LYN-1604LYN-1604 is a potential ULK1 agonist with IC50 of 1.66 μM against MDA-MB-231 cells and it binds to wild-type ULK1 with a binding affinity in the nanomole range (Kd=291.4 nM). The ULK1 (Y89A) mutant protein caused a sharp decrease in binding affinity with lower response and Kd than wild-type ULK1, ULK1 (K50A) and ULK1 (L53A) mutants. |
||
| S7779 |
Smoothened Agonist (SAG) HClSmoothened Agonist (SAG) HCl is a cell-permeable Smoothened (Smo) agonist with EC50 of 3 nM in Shh-LIGHT2 cells. |
Activating Shh signaling by SAG injection in naïve mice significantly increased BDNF expression, and pretreatment with cyclopamine effectively prevented the upregulation of BDNF induced by SAG (E). Tissues were collected at 2 hours after SAG injection. Six mice were included in each group.
|
| Catalog No. | 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. |
SMOΔC captured on cholesterol beads in the presence of increasing concentrations of free vismodegib or 20(S)-OHC (h). Results from one of two independent pull-down experiments are shown. |
|
| S2157 |
Taladegib (LY2940680)Taladegib (LY2940680) binds to the Smoothened (Smo) receptor and potently inhibits Hedgehog (Hh) signaling. Phase 1/2. |
||
| S8075 |
GANT61GANT61 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. |
Apoptosis evaluation of UACC62R, SK-MEL-28 R and R3 cells treated with Gant61 (10 μM) for 48 h by flow cytometry detection of Annexin V staining. |
|
| S8200 |
MK-4101MK-4101, a potent inhibitor of the Hedgehog pathway, shows anti-tumor activity through the inhibition of proliferation and induction of extensive apoptosis in tumor cells. |
||
| S8249 |
HPI-4 (Ciliobrevin A)HPI-4 (Ciliobrevin A) is a hedgehog (Hh) pathway antagonist. It blocks Sonic hedgehog (Shh)-induced Hh pathway activation (IC50 = 7 μM) downstream of Smo. |
||
| S4747 |
JervineJervine is a Hedgehog signaling (IC50=500-700 nM) inhibitor that inhibits the sonic hedgehog (shh) pathway by interacting with smoothened. |
||
| S7160 |
Glasdegib (PF-04449913)Glasdegib (PF-04449913) is a potent, and orally bioavailable Smoothened (Smo) inhibitor with IC50 of 5 nM. Phase 2. |
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S1146 |
CyclopamineCyclopamine is a specific Hedgehog (Hh) signaling pathway antagonist of Smoothened (Smo) with IC50 of 46 nM in TM3Hh12 cells. |
2015, 10.1038/nature14325 2018, 97(6):1235-1243 2012, 14(12):1441-51 |
(A)[3H]thymidine incorporation assay of B16F10 melanoma cells treated with DMSO or cyclopamine after incubation with SA-CM from WT and Cav1KO dermal fibroblasts. Representative phase-contrast images of B16F10 cells treated with SA-CM from WT and Cav1KO fibroblasts with cyclopamine are shown on the right. Similar experiments (B) were done with A-375 cells incubated with SA-CM from hTBJ1-shCtrl and hTBJ1-shCAV1 cells. |
| S2151 |
Sonidegib (Erismodegib, NVP-LDE225)Sonidegib (Erismodegib, NVP-LDE225) 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. |
2016, 127(10):1325-35 2013, 9(4):247-9 2015, 21(20):4686-97 |
RU-SKI 43 blocks Shh signaling. (a) RU-SKI 43 blocks Gli activation. NIH 3T3 cells were cotransfected with vectors encoding 8× Gli-binding site (GliBS)-Firefly luciferase (unless indicated otherwise), Renilla luciferase reporter (pRL-TK) and Shh. Confluent cells were treated with DMSO, 10 μM LDE225, 10 μM RU-SKI 43 or 10 μM C-2. The firefly luciferase (FL)/Renilla luciferase (RL) ratio in cell lysates was calculated and normalized to that measured in DMSO-treated samples; error bars represent mean ± s.d. (n = 2–3). |
| S2777 |
PF-5274857PF-5274857 is a potent and selective Smoothened (Smo) antagonist, inhibits Hedgehog (Hh) signaling with IC50 and Ki of 5.8 nM and 4.6 nM, respectively, and can penetrate the blood–brain barrier. |
||
| S7092 |
SANT-1SANT-1 directly binds to Smoothened (Smo) receptor with Kd of 1.2 nM and inhibits Smo agonist effects with IC50 of 20 nM. |
2019, 10.1039/c8lc01298a |
(D) Percentage cell death of OCI-AML3 cells was measured using the CellTiter-Glo® viability assay following 24 hours treatment with either sequential treatment of 1 μM Vorinostat with low (0.1 μM) or high dose (2.5 μM) SANT-1, or single agents. Data represents a biological replicate of 3, with data presented relative to the DMSO control (0% cell death). (E) Protein expression of SHH was measured following 24 hours treated with the four treatment strategies in OCI-AML3 cells. Equal loading was confirmed with β-Actin |
| S7138 |
BMS-833923BMS-833923 is an orally bioavailable Smoothened antagonist. Phase 2. |
2015, 17(7):538-51 2018, 1148-1154 2017, 7(1):1899 |
Cell viability assays performed on H1650 and H1975 cells with various concentrations of BMS-833923 (B).
|
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S3042 |
PurmorphaminePurmorphamine, 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. |
2018, 189:23-36 2017, 385:128-136 2017, 36(1):23 |
a-d) LoVo cells were separately or simultaneously treated with 1 μM purmorphamine and 1 μM thiostrepton for the indicated time. a The Gli1, FoxM1, and CCNB1 protein expression levels were examined by immunoblotting after drug treatment for 48 h. b Cell viability was detected after 6 days using an MTT assay. c LoVo cells treated with indicated drugs were cultured for 2 weeks, and outgrowth colonies were stained with crystal violet. d The matched colony count of (c). Error bars represent the mean and S.D. of three independent experiments. **, p < 0.01.
|
| S8597 |
LYN-1604LYN-1604 is a potential ULK1 agonist with IC50 of 1.66 μM against MDA-MB-231 cells and it binds to wild-type ULK1 with a binding affinity in the nanomole range (Kd=291.4 nM). The ULK1 (Y89A) mutant protein caused a sharp decrease in binding affinity with lower response and Kd than wild-type ULK1, ULK1 (K50A) and ULK1 (L53A) mutants. |
||
| S7779 |
Smoothened Agonist (SAG) HClSmoothened Agonist (SAG) HCl is a cell-permeable Smoothened (Smo) agonist with EC50 of 3 nM in Shh-LIGHT2 cells. |
2017, 545(7652):54-59 2013, 58(5):1801-13 2018, 11:649-659 |
Activating Shh signaling by SAG injection in naïve mice significantly increased BDNF expression, and pretreatment with cyclopamine effectively prevented the upregulation of BDNF induced by SAG (E). Tissues were collected at 2 hours after SAG injection. Six mice were included in each group.
|
