Structure-based screening and a conformational biosensor identify a GPR183 inverse agonist and an activation switch
Louise Andersson, Michele Roggia, Kittikorn Wangriatisak, Rhiannon Skye Kozel, Holly R. Brittain, Sonia Youhanna, Maria Gil, Mathias Haag, Volker M. Lauschke, Karine Chemin, Sandro Cosconati, Paweł Kozielewicz · 2026
Read Structure-based screening and a conformational biosensor identify a GPR183 inverse agonist and an activation switch by Louise Andersson, Michele Roggia, Kittikorn Wangriatisak, Rhiannon Skye Kozel, Holly R. Brittain, Sonia Youhanna, Maria Gil, Mathias Haag, Volker M. Lauschke, Karine Chemin, Sandro Cosconati, Paweł Kozielewicz (2026) in the Tower of Babel, a free online library of public-domain works preserved in clean, searchable text. No sign-up. The full text is served as a plain-text file at a predictable URL, where text is present: https://antarctic-labs.com/tower-of-babel/pmc-13392048.txt.
Description
Louise Andersson's team used AI-driven virtual screening to find inverse agonists for GPR183, a chemotactic sensor guiding immune cell migration. From seventy compounds plus hit expansion, compound 78 emerged as a potent blocker of both constitutive and agonist-driven Gi signals and beta-arrestin recruitment.
A conformational biosensor, small-scale dynamics, and mutagenesis proved binding within the sensor core. The compound blocked agonist-driven migration of human blood single-nucleus cells ex vivo with very high potency. Mutating tyrosine 260 in helix six altered efficacy and induced signals bias, revealing an activation switch for future immune, autoimmune, and cancer drug design.
Catalog record
| CREATOR | Louise Andersson, Michele Roggia, Kittikorn Wangriatisak, Rhiannon Skye Kozel, Holly R. Brittain, Sonia Youhanna, Maria Gil, Mathias Haag, Volker M. Lauschke, Karine Chemin, Sandro Cosconati, Paweł Kozielewicz |
|---|---|
| YEAR | 2026 |
| COLLECTION | PAPERS |
| FORMAT | TXT |
| FILE SIZE | 113 KB |
| VERSION | 1.0 |
| LICENSE | CC BY 4.0 |
| RIGHTS | CC BY |
| SOURCE | Europe PMC |