Enzo Life Sciences Leading Light Sclerostin-LRP Screening System

Thursday, 14 November, 2013 | Supplied by: United Bioresearch Products Pty Ltd

Enzo Life Sciences has expanded its portfolio of Wnt Pathway assays with the Leading Light Sclerostin-LRP Screening System. The simple, rapid biochemical binding assay format does not require cell lines or transfection reagents, making it a convenient platform for initial screening of inhibitors of the Wnt antagonist sclerostin.

The screening system is a 96-well plate assay based on sclerostin-LRP interaction. It contains engineered LRP5-alkaline phosphatase (ALP) and human sclerostin immobilised in a multiwell 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.

The reproducible, high-throughput amenable assay (Z’-factor 0.871) can be used for drug screening to identify small molecule compounds, antibodies, DNA aptamers and peptides capable of modulating sclerostin-LRP interaction. It has a high-sensitivity chemiluminescent readout (signal-to-noise ratio of ≥ 10) and its rapid protocol yields results in just 2.5 h.

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 signalling 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. Clinical trial studies demonstrate that antibodies against sclerostin can also increase human bone mineral density; thus, sclerostin is thought to be a superior therapeutic target for osteoporosis treatment over current methods such as treatment with bisphosphonate derivatives.

Online: www.unitedbioresearch.com.au
Phone: 02 4575 0309
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