LEADING LIGHT^® Sclerostin-LRP Interaction Screening System

• High sensitivity chemiluminescent readout (signal-to-noise ratio of ≥ 10)
• Rapid protocol yields results in just 2.5 hours
• No cell lines or transfection reagents required
• Reproducible, high-throughput amenable assay (Z’-factor 0.871)
• Amenable for high-throughput screening applications

The LEADING LIGHT^® Sclerostin Screening System is a 1×96 well plate assay based on Sclerostin–LRP interaction. This system contains engineered LRP5-alkaline phosphatase (ALP) and human Sclerostin immobilized in a multi-well plate. LRP5-alkaline phosphatase binds to Sclerostin coated on the bottom of the well and is detected by the activity of alkaline phosphatase remaining after a washing step. This system can be used for drug screening to identify small molecule compounds, antibodies, DNA aptamers and peptides capable of modulating sclerostin-LRP interaction.

Sclerostin is encoded by the SOST gene and serves as a negative regulator of bone formation. Wnt ligands bind to Frizzled (Fz) and LRP5/6 receptors to trigger the canonical Wnt signaling cascade, which has been reported to play an important role in bone development. Sclerostin can bind to LRP5/6 to inhibit the canonical Wnt signaling. Antibodies against Sclerostin can block Sclerostin-mediated Wnt inhibition in cell based assays and increase bone mineral density in animal models. Importantly clinical trial studies demonstrate that antibodies against Sclerostin can also increase human bone mineral density. Consequently, Sclerostin is thought to be a superior therapeutic target for osteoporosis treatment over current implemented methods such as treatment with bisphosphonate derivatives.