March 17, 2025publication

GPR75 cryo-EM structure unlocks small-molecule discovery

First reported cryo-EM structure of an EMP-stabilised GPR75 enables in silico screening of inverse-agonist scaffolds for obesity.

Abilita's structural biology team determined the first cryo-EM structure of the orphan GPCR GPR75 in an inactive, EMP-stabilised state. GPR75 has been validated through human genetics as a target for obesity — loss-of- function mutations correlate with lower BMI — but historically defied structural characterisation.

The structure has enabled in-silico screening of multiple small-molecule families, with lead candidates expected in 2H 2026.