PROFILING ESTABLISHED CELL-LINES AS A MEANS TO SCREENING DIVERSITY

Cell lines provide a readily available source of target material for f unctional and molecular binding screens in drug discovery. The Cell PR OFILE(R) program at NovaScreen(TM) represents an effort to identify re ceptors and enzymes expressed in established cell lines that are relev ant to important drug screening endeavors. In this report, we present data on a selected number of receptors and enzymes for four cell lines studied in this survey. The objective of this survey was not to compa re one cell line with another, but to illustrate the diversity of phar macologic targets and the untapped potential of databases for readily obtainable cell lines. The following cell lines, which are all derived from human tumors, were included in this study (with some relevant ph armacologic/pathologic targets): HT-29, derived from an adenocarcinoma of the colon (colorectal cancer); SK-N-MC, derived from a neuroepithe lioma (NPY receptors, apoptosis, HIV type I infection); H-4, derived f rom a neuroglioma (Alzheimer's disease); and LNCaP, derived from a pro state carcinoma (androgen receptor, prostate cancer). Specific to this survey were receptor-binding assays for androgens, corticotropin-rele asing factor, endothelin, GABA, NMDA, somatostatin, and alpha and beta adrenergic ligands, as well as binding sites for ion channels. A comp arison of specific binding of these various sites between target tissu es routinely used in our assays and established cell lines reveals a d iversity of receptors heretofore not reported for the latter and repre sents a potential database for screening and pharmacologic research.