Biophysical Society Thematic Meeting | Bucharest 2026

Biophysics of Membrane Reactions in Brian

Thursday Speaker Abstracts

SOMETHING SWEET A TALE OF A NOVEL MODULATOR FOR FREE FATTY ACID RECEPTOR (FFAR1/GPR40) Cosmin Trif 1 ; Teodor Asvadur Sulea 2 ; Sorina Andreea Anghel 1 ; Laurentiu Spiridon 2 ; Andrei José Petrescu 2 ; Sorin Tunaru 1 ; 1 Institute of Biochemistry of the Romanian Academy, Cell Signaling , Bucharest, Romania 2 Institute of Biochemistry of the Romanian Academy, Bioinformatics , Bucharest, Romania Objective Free fatty acid receptor 1 (FFAR1/GPR40) is protein of a 4-membered family of receptors that respond to fatty acids which modulates glucose stimulated insulin secretion (GSIS). Diabetes mellitus (DM) can lead to a decrease GSIS. DM type 2 is caused by a reduction of insulin secretion, insulin resistance in peripheral tissues and inflammation. Since the failure in phase III clinical trial of TAK-875, a potent agonist of FFAR1 in the nanomolar range, we have attempted to find a novel modulator of FFAR1 with a different chemical scaffold than has been previously used, which drove pharmaceutical chemists to design and synthethize modulators by bioisosteric replacement substitution of the carboxylic group or the large lipophilic tail of lipids. Methods Both in vitro and in silico approaches have been used in the present study. Regarding the dry lab Molecular Docking , Molecular Dynamics, Homology Modeling was used. In the wet lab we employed overexpression of this receptor in immortalized cell lines HEK293T(they don't express endogenously FFAR1) and in order to further validate the molecule we used INS-1E. In both cases we used G5A a well known intracellular biosensor. We also determined GSIS using various assays Results The ligand induced a rise in intracellular calcium concentration upon activation of FFAR1 and this signaling led to a an increase of GSIS Conclusions At the time of writing, a potential hit has been found and is waiting for further optimization into a number of lead compounds. Bibliography Offermanns, S. (2025). Regulation of Insulin Secretion Through Long ‐ Chain Fatty Acid Receptors. iNew Medicine, e70006. Acknowledgements - This work was funded by This research was supported by The Ministry of Investments and European Projects, through the Managing Authority for the Health Program, PS/272/PS_P5/OP1/RSO1.1/PS_P5_RSO1.1_A9–ROGEN Project (MySMIS 324809) and The Romanian Academy. and CNCS - UEFISCDI, project number PN-III-P2-2.1 PED-2019-5179

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