Researchers used a yeast-based SPS system to identify atazanavir as a pan-PAM for family A GPCRs. It acts as a molecular glue, stabilizing a non-canonical megacomplex through pendulum engagement of β-arrestin, leading to sustained G protein signaling from endosomes.

References:

• He G, Sun Q, Xu X, et al. A GPCR-G protein-β-arrestin megacomplex enabled by a versatile allosteric modulator[J]. Cell, 2026.