Selective positive allosteric modulation of β2AR using antibody fragments targeting the third intracellular loop

Edgardo J. Sánchez Rivas; Fredrik Sadler; Mohammadamin Safdari; Nishaben Patel; Michael Ritt; Ning Ma; Sergio Branciamore; Nagarajan Vaidehi; Sivaraj Sivaramakrishnan

doi:10.1038/s41467-026-72785-y

May 6, 2026Nature CommunicationsOpen Access

Selective positive allosteric modulation of β2AR using antibody fragments targeting the third intracellular loop

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Key Points

The aim is to demonstrate the potential of selectively modulating β2AR using antibody fragments targeting its divergent loop region.
Utilized antibody fragments targeting the third intracellular loop of β2AR.
Assessed ligand-induced cAMP accumulation.
Investigated receptor internalization mechanisms.
Demonstrated increased ligand-induced cAMP accumulation.
Confirmed selective modulation of β2AR through targeted antibody fragments.

Implication

Demonstrates selective allosteric modulation in GPCRs, suggesting new therapeutic approaches.

Abstract

AR internalization promoting greater ligand-induced accumulation of cAMP. Our study demonstrates proof-of-concept for selective allosteric modulation of a GPCR by targeting a sequence divergent loop region within the receptor fold.

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Cite This Study

Rivas et al. (2026) studied this question.

synapsesocial.com/papers/69fececcb9154b0b8287611e https://doi.org/10.1038/s41467-026-72785-y

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Selective positive allosteric modulation of β2AR using antibody fragments targeting the third intracellular loop

Key Points

Implication

Abstract

Discussion

Cite This Study

Selective positive allosteric modulation of β2AR using antibody fragments targeting the third intracellular loop

Key Points

Implication

Abstract

Discussion

Cite This Study

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