GtoPdb Ligand ID: 9686

Synonyms: GSK-2894512 | GSK2894512 [2] | WB-1001 | WBI 1001 | WBI-1001
Compound class: Synthetic organic
Comment: Tapinarof (GSK2894512) is an aryl hydrocarbon receptor (AhR) agonist [2]. It is a natural product derived from bacteria that exist symbiotically with entomopathogenic nematodes. AhR was identified as the primary molecular target based on phenotypic screening using the DiscoveRx BioMAP Diversity Plus System and confirmed using AhR knockout mice.
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 0
Hydrogen bond donors 2
Rotatable bonds 3
Topological polar surface area 40.46
Molecular weight 254.13
XLogP 5.04
No. Lipinski's rules broken 1
Canonical SMILES CC(c1c(O)cc(cc1O)C=Cc1ccccc1)C
Isomeric SMILES CC(c1c(O)cc(cc1O)/C=C/c1ccccc1)C
InChI InChI=1S/C17H18O2/c1-12(2)17-15(18)10-14(11-16(17)19)9-8-13-6-4-3-5-7-13/h3-12,18-19H,1-2H3/b9-8+
No information available.
Summary of Clinical Use
Topically applied tapinarof (research code GSK2894512) has shown clinical efficacy in Phase 2 clinical trial in patients with plaque psoriasis [1] (NCT02564042). A Phase 3 trial (NCT03202004) is ready to recruit subjects (Oct 2017). Tapinarof has also completed Phase 1 studies for atopic dermatitis.
Mechanism Of Action and Pharmacodynamic Effects
The AhR is a cytosolic ligand-activated transcription factor that senses a wide range of endogenous and exogenous molecules and influences multiple biological activities. IIn the immune system it acts as a regulator of innate and adaptive immune responses, impacting the balance of Th17 and Treg cells. Tapinarof modulates the immune response via an agonistic interaction with the AhR [2].