title: Adventures in drug discovery: potent agents based on ligands for cell-surface receptors.
abstract: How does one go about discovering new drugs? This question is addressed by descriptions of drug discovery research in three project areas that pertain to antagonist ligands for cell-surface receptors. The molecular targets of interest are protease-activated receptor-1 (PAR-1), vasopressin receptors (V1a and V2 subtypes), and the fibrinogen receptor (GPIIb/IIIa). I present different approaches to the identification of high-affinity ligands for these receptors, en route to drug candidates. The PAR-1 project resulted in a pharmacological tool compound that facilitated in vivo proof-of-principle studies, whereas the vasopressin and fibrinogen receptor projects resulted in several preclinical development compounds, three of which advanced into human clinical trials.
authors.affiliation: Vascular Research Team, Johnson & Johnson Pharmaceutical Research & Development, Spring House, Pennsylvania 19477-0776, USA. bmaryano@prdus.jnj.com
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Maryanoff
mesh_terms: D000818:Animals; D015195:Drug Design; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D044463:Receptor, PAR-1 / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D039341:Receptors, Fibrinogen / Q000378:metabolism*; D017483:Receptors, Vasopressin / Q000378:metabolism*
chemical_list: D008024:Ligands; D044463:Receptor, PAR-1; D011956:Receptors, Cell Surface; D039341:Receptors, Fibrinogen; D017483:Receptors, Vasopressin