Target family: Class Frizzled GPCRs (type: gpcr)
Target: SMO

Ligand: vismodegib (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (2012), EMA (2013)
Primary target: yes
Median affinity: 7.789999961853027 pKi
Reference (Journal): Identification of a novel Smoothened antagonist that potently suppresses Hedgehog signaling.
Published in: Bioorg Med Chem

Ligand: taladegib (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 8.199999809265137 pIC50
Reference (Journal): Design, synthesis, and biological evaluation of optimized phthalazine derivatives as hedgehog signaling pathway inhibitors.
Published in: Eur J Med Chem

Ligand: TAK-441 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 8.359999656677246 pIC50
Reference (Journal): Discovery of the investigational drug TAK-441, a pyrrolo[3,2-c]pyridine derivative, as a highly potent and orally active hedgehog signaling inhibitor: modification of the core skeleton for improved solubility.
Published in: Bioorg Med Chem

Ligand: sonidegib (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: EMA & FDA (2015)
Primary target: yes
Median affinity: 8.220000267028809 pKi
Reference (Journal): Identification of a novel Smoothened antagonist that potently suppresses Hedgehog signaling.
Published in: Bioorg Med Chem

Ligand: saridegib (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: yes
Median affinity: 8.850000381469727 pIC50
Reference (Journal): Discovery of a potent and orally active hedgehog pathway antagonist (IPI-926).
Published in: J Med Chem

Ligand: SANT-2 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 7.519999980926514 pIC50
Reference (Journal): Small molecule modulation of Smoothened activity.
Published in: Proc Natl Acad Sci USA

Ligand: SANT-1 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 7.699999809265137 pKi
Reference (Journal): Small molecule modulation of Smoothened activity.
Published in: Proc Natl Acad Sci USA

Ligand: SAG1.3 (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity: 8.520000457763672 pEC50
Reference (Journal): Small molecule modulation of Smoothened activity.
Published in: Proc Natl Acad Sci USA

Ligand: purmorphamine (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity: 6 pEC50
Reference (Journal): Purmorphamine activates the Hedgehog pathway by targeting Smoothened.
Published in: Nat Chem Biol

Ligand: GSA-10 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Primary target: no
Median affinity: 5.920000076293945 pEC50
Reference (Journal): Discovery, molecular and pharmacological characterization of GSA-10, a novel small-molecule positive modulator of Smoothened.
Published in: Mol Pharmacol

Ligand: MRT-92 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 9.520000457763672 pKd
Reference (Journal): MRT-92 inhibits Hedgehog signaling by blocking overlapping binding sites in the transmembrane domain of the Smoothened receptor.
Published in: FASEB J

Ligand: glasdegib (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (2018), EMA (2020)
Primary target: yes
Median affinity: 8.300000190734863 pIC50
Reference (Journal): Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
Published in: ACS Med Chem Lett

Ligand: cyclopamine-KAAD (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 7.699999809265137 pIC50
Reference (Journal): Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine.
Published in: Nature

Ligand: cyclopamine (Natural product)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 7 pIC50
Reference (Journal): Cyclopamine bioactivity by extraction method from Veratrum californicum.
Published in: Bioorg Med Chem

Ligand: AZD8542 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: yes
Median affinity: 8.520000457763672 pIC50
Reference (Webpage): AZD8542.

Ligand: AZD8542 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 8.819999694824219 pIC50
Reference (Webpage): AZD8542.

Ligand: ANTA XV (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 8.149999618530273 pIC50
Reference (Journal): Synthesis and evaluation of novel benzylphthalazine derivatives as hedgehog signaling pathway inhibitors.
Published in: Bioorg Med Chem Lett