Additional Research Compound · For laboratory research use only
WAY-316606 (5-(benzenesulfonyl)-N-piperidin-4-yl-2-(trifluoromethyl)benzenesulfonamide) is a small-molecule inhibitor of secreted frizzled-related protein 1 (sFRP-1), an endogenous antagonist of Wnt signalling. It was developed at Wyeth from a high-throughput screen of more than 440,000 compounds, as a lead from the diphenylsulfonyl sulfonamide series1,2.
It was originally studied in bone formation models1, and has since been used as a pharmacological tool to probe sFRP-1 function in ex vivo human hair follicle organ culture, osteoclast differentiation, neural progenitor activation, spinal cord injury biomaterials and melanoma cell lines3,4,5,6,7. All published work is preclinical.
As described in the research literature
As described in the research literature, sFRP-1 binds Wnt ligands and prevents them from activating their Frizzled receptors. In the discovery work, WAY-316606 bound sFRP-1 in a tryptophan fluorescence quenching assay and inhibited it in a cell-based TCF-luciferase reporter assay of canonical Wnt signalling1. Structure-activity relationships for the scaffold were reported separately2.
Because sFRP-1 inhibition only permits signalling by Wnt ligands already present, the hair follicle study described the approach as ligand-limited; in that work, sFRP-1 was identified by microarray as down-regulated in the dermal papilla of cyclosporine A-treated scalp follicles, and WAY-316606 was used to examine intrafollicular canonical Wnt/β-catenin activity3. In osteoclast cultures, a separate group reported that both extracellular and intracellular sFRP-1 could block canonical Wnt signalling, and that WAY-316606 reversed this through what the authors termed dual modulation4.
What published studies have examined
The discovery study measured total bone area in a murine calvarial organ culture assay1. Later work examined osteoclastogenesis, bone resorption and osteoclast-specific gene expression in vitro, and bone loss in an ovariectomised mouse model4.
Human scalp hair follicles maintained ex vivo were used to examine hair shaft production, hair shaft keratin expression and spontaneous follicle regression (catagen) with WAY-3166063. The same study examined canonical Wnt/β-catenin activity in the hair bulb3.
Sources [3]
Single-cell RNA sequencing of progenitors from the aged human subventricular zone identified sFRP-1 as a candidate quiescence signal, and WAY-316606 was used to examine neural stem cell activation in vitro and in mice5. A rat spinal cord injury study incorporated WAY-316606 into a composite hydrogel and examined neural stem cell recruitment, neuronal differentiation and motor function6.
A 2026 study measured sFRP-1 expression in metastatic melanoma cell lines and xenografts, and examined WAY-316606 for effects on cell viability, cell cycle, migration, invasion and extracellular matrix gene expression, with sFRP-1 knockdown as a comparison7.
Sources [7]
A small molecule inhibitor of the Wnt antagonist secreted frizzled-related protein-1 stimulates bone formation.
Bodine PV, Stauffer B, Ponce-de-Leon H, et al. Bone, 2009.
Modulation of Wnt signaling through inhibition of secreted frizzled-related protein I (sFRP-1) with N-substituted piperidinyl diphenylsulfonyl sulfonamides.
Moore WJ, Kern JC, Bhat R, et al. Journal of Medicinal Chemistry, 2009.
Identifying novel strategies for treating human hair loss disorders: Cyclosporine A suppresses the Wnt inhibitor, SFRP1, in the dermal papilla of human scalp hair follicles.
Hawkshaw NJ, Hardman JA, Haslam IS, et al. PLoS Biology, 2018.
The SFRP1 Inhibitor WAY-316606 Attenuates Osteoclastogenesis Through Dual Modulation of Canonical Wnt Signaling.
Ma Q, Wang S, Xie Z, et al. Journal of Bone and Mineral Research, 2022.
Single-cell profiling of human subventricular zone progenitors identifies SFRP1 as a target to re-activate progenitors.
Donega V, van der Geest AT, Sluijs JA, et al. Nature Communications, 2022.
Double crosslinked biomimetic composite hydrogels containing topographical cues and WAY-316606 induce neural tissue regeneration and functional recovery after spinal cord injury.
Zhao X, Lu X, Li K, et al. Bioactive Materials, 2022.
Targeting sFRP1 with WAY-316606 Suppresses Proliferation, Migration, and Invasion in Metastatic Melanoma.
Kim D, Park J, Na O, et al. Cancers, 2026.
This page is provided for research and educational reference only. It does not constitute medical advice, dosing guidance, or a recommendation for use. All compounds are strictly for laboratory and in-vitro research purposes.