ASICs are potential drug targets of interest. Their activation mechanism has however remained elusive. ASICs are neuronal, proton-gated, sodium-permeable channels that are expressed in the central and peripheral nervous system of vertebrates. They form a subfamily of the Epithelial Na…
Blog Archives
Hot topic: Engineered mini G proteins provide a useful tool for studying the activation of GPCRs in living cells
In order to stabilize the GPCR-G protein complex, an agonist must be bound to the receptor and the alpha subunit of the heterotrimer must be in a nucleotide-free state. Ground-breaking work by expert crystallographers made use of so-called mini G…
Hot Topic: Unexplored therapeutic opportunities in the human genome
Contemporary drug discovery is dominated by two related themes. The first of these is target validation upon which the sustainability of pharmaceutical R&D (in both the commercial and academic sectors) crucially depends. The second is the size of the pool of human…
Hot topic: The G Protein-Coupled Receptors deorphanization landscape.
Within the vast GPCR superfamily, orphans are described as receptors devoid of known endogenous ligands. They have been labeled as 7 transmembrane proteins by sequence homology and dispatched accordingly in the different GPCR subfamilies. They have attracted much attention given…
Hot topic: Pharmacogenomics of GPCR Drug Targets
A system of rigorous clinical trials and regulation exist to ensure that a new drug is safe and effective when reaching the market. However, natural human genetic variation(s) may cause individuals to respond differently to the same medication. A collaboration…
Hot topic: Trends in GPCR drug discovery: new agents, targets and indications
New avenues for GPCR drug discovery have emerged owing to recent advances in receptor pharmacology, technological breakthroughs in structural biology and innovations in biotechnology. A collaboration between the Department of Drug Design and Pharmacology, University of Copenhagen (home of the…
Hot topic: Cryo-EM structures of Mucolipin TRP Channels in the Lysosome: Five Together at Once
The mucolipin subfamily of Transient Receptor Potential (TRP) channels, which consist of TRPML1, TRPML2, and TRPML3 (a.k.a. MCOLN1- 3), are Ca2+-permeable cation channels localized in intracellular endosomes and lysosomes. In response to cellular stimulation, TRPMLs mediate Ca2+ release from the…
