Screening Natural Small Molecular Regulators Of Target Nuclear Receptor RXR? And Study Of Its Biological Function

Nuclear hormone receptors(NHRs)represent one of the most important drug targets.Retinoid X receptor(RXR)is a member of the nuclear receptor superfamily and becomes a therapeutic target because it is a heterodimer partner of many nuclear receptors,controls almost aspects of biological processes and is highly related to pathological conditions,such as cancers and other diseases.Natural small molecular regulators which used in targeted therapy are developed from the molecular mechanism.Therefore,compared with traditional drugs,they have better selectivity and fewer side effects in tumor cells attack.Using structure-based targeted design strategy to design compounds will increase the hit rate of active compounds and reduce the cost of the synthesis and screening of a large number of compounds.We screened that a number of pure compounds significantly caused tumor cells death via combining with RXR then inhibited the growth of tumor cells and induce apoptosis of tumor cells.In order to understand its chemical constituents,the chemical constituents of the 65%ethanol extract of Fructus Podophylli were studied.Three compounds were isolated by column chromatographic methods such as silica gel and HPLC(High Performance Liquid Chromatography).On the basis of NMR(Nuclear Magnetic Resonance)analysis,the structures of compound 1,2 and 3 were determined.RXR binding assay and dual luciferase reporter gene were employed to screen compounds that target at RXR.Growth suppression was detected by MTT assay.We got one natural small molecular regulator by purify the single component step by step according to the results of activity screening.