We propose to develop a novel technique for the identification of clinically relevant target proteins for botanical extracts. This method will help to understand the biological mechanisms of action of botanical drugs. The technique is based on display cloning, a selection procedure using phage display and affinity chromatography. Published results have shown that display cloning can afford cellular target proteins for non-peptidic, small organic molecules. Initially, display cloning will be used to identify target proteins for a selected group of natural products with different binding affinities for their known receptors. After demonstrating feasibility, a chemical tagging procedure will be developed that will allow the determination of cellular binding proteins for whole botanical extracts, without the isolation of individual compounds. Using randomly primed cDNA libraries, cellular targets may be full-length proteins or ligand-binding domains. The first application for this innovative method will be the development of a botanical drug with effectiveness against post-menopausal symptoms, currently treated with estrogen supplementation. The proposed method will have a significant impact on product development, namely the detailed characterization, manufacturing and quality control of standardized, efficacious and safe botanical drugs. It will provide immediate access to bioassay development and intellectual property for patentable manufacturing procedures.
This novel target-protein identification technology will help to elucidate the biological mechanism of action of botanical extracts and will serve primarily as a proprietary method for the identification and characterization of botanical medicines. It's first application will be the development of a new, FDA approved botanical drug against post-menopausal symptoms, based on the plant extract of Black cohosh, currently a dietary supplement and the 3rd fastest growing herbal product in the mass market (>500%), after Green tea (?1,000%), and St. John's wort (2, 800%).
| Boehmerle, Wolfgang; Splittgerber, Ute; Lazarus, Michael B et al. (2006) Paclitaxel induces calcium oscillations via an inositol 1,4,5-trisphosphate receptor and neuronal calcium sensor 1-dependent mechanism. Proc Natl Acad Sci U S A 103:18356-61 |
