IUPHAR-DB: updated database content and new features

Abstract

The International Union of Basic and Clinical Pharmacology (IUPHAR) database, IUPHAR-DB (http://www.iuphar-db.org) is an open access, online database providing detailed, expert-driven annotation of the primary literature on human and rodent receptors and other drug targets, together with the substances that act on them. The present release includes information on the products of 646 genes from four major protein classes (G protein-coupled receptors, nuclear hormone receptors, voltage- and ligand-gated ion channels) and ∼3180 bioactive molecules (endogenous ligands, licensed drugs and key pharmacological tools) that interact with them. We have described previously the classification and curation of data for small molecule ligands in the database; in this update we have annotated 366 endogenous peptide ligands with their amino acid sequences, post-translational modifications, links to precursor genes, species differences and relationships with other molecules in the database (e.g. those derived from the same precursor). We have also matched targets with their endogenous ligands (peptides and small molecules), with particular attention paid to identifying bioactive peptide ligands generated by post-translational modification of precursor proteins. Other improvements to the database include enhanced information on the clinical relevance of targets and ligands in the database, more extensive links to other databases and a pilot project for the curation of enzymes as drug targets.

A luminescent assay for real-time measurements of receptor endocytosis in living cells

“…To demonstrate potential suitability for profiling of receptor antagonists in a screening format, inhibition of Nluc-β2AR was measured using a panel of β2AR blockers in the presence of a fixed concentration (1 µM) ISO (Fig 1c). Rank-order potency of the antagonist panel was closely aligned with pharmacological profiling of ligand affinity at β2AR by traditional methods [16][17][18] observed for the Nluc-HaloTag® fusion with results similar to those obtained using Nluc alone (Fig. 2a).…”

Physiological effects and therapeutic potential of proinsulin C-peptide

“…To identify candidate C-peptide receptors, we used the Deductive LigandReceptor Matching Strategy developed by our laboratory to identify the receptor for the neuropeptide neuronostatin (114). We first screened three cell lines found to respond to C-peptide, including the human erythroleukemia cell line TF-1, the human embryonic kidney cell line HEK 293, and the human gastric tumor cell line KATOIII, for the expression of all known orphan GPCRs, as catalogued by IUPHAR (93). We found that 24 of the ϳ136 orphan GPCRs were expressed by TF-1, HEK 293, and KATOIII cells.…”

G protein-coupled receptors in energy homeostasis

“…The neuropeptide Y system, comprising neuropeptide Y (NPY), peptide YY (PYY), pancreatic polypeptide (PP) and the corresponding Y receptors (Y1, Y2, Y4, Y5 and Y6), is well known for its role in the regulation of energy homeostasis and associated processes [52,53]. NPY, PYY and PP have been classified into a family of homologous peptides because of their sequence homology and common tertiary structural motif, a hairpin fold [54].…”