Project: Biotechnological platform for “in silico” and “in vitro” High Throughput Screening of Muscarinic Receptors ligands.

G-protein-coupled receptors (GPCRs) are considered as one of the main therapeutic targets for a large set of pathologies. Indeed, several diseases such as cancer or neurodegenerative diseases are characterized by the alteration in the density or function of different GPCRs like muscarinic acetylcholine receptors (mAChRs). One of the main problems in the finding of new ligands for mAChRs, is that can be coupled to different G proteins. Therefore, the aim of this project is to create a platform for the high throughput screening (HTS) “in silico” and “in vitro” of mAChRs ligands as well as for the production of subtype specific antibodies against mAChRs. For this purpose, Intelligent Pharma will create a QSAR software that enables the “in silico” prediction of the selectivity and specificity of mAChR molecules using pharmacological parameters obtained from the analysis of muscarinic ligands in cell membrane microarrays (CMM) specifically developed by IMG Pharma for the “in vitro” HTS. CMM will consist of membranes obtained from mammalian cell lines that overexpress a mAChR together with a specific G protein (created by Delphi Genetics) as well as another set of GPCRs to determine the specificity of the tested compounds. Thus, CMM could be used for the pharmacological characterization of primary and secondary targets of a tested compound, and therefore for the prediction of its safety profile. Once developed the software platform, Intelligent Pharma will proceed to screen "in silico" a library of compounds, which will be validated "in vitro" again using microarrays. In addition, Delphi Genetics will generate antibodies against mAChRs, which will be validated in their cell lines and in CMM. However, fluoro or radiolabeled compounds are need in these assays, with the correspond disadvantages. Thus, the development of non-labeled methods (Mass Spectrometry) to detect molecules will be of great interest not only for this project but also to the pharmaceutical industry.

Acronym HTScreenTECH
Network ETB-PRO
Call 8th call for proposals (Call 2013)

Project partner

Number Name Role Country
IMG Pharma Biotech Coordinator Spain
Belgium Belgium