Pina Cardarelli, CSO of GPCR Therapeutics.

Devki D Sukhtankar and Pina M Cardarelli's research: Burixafor Hydrobromide (GPC-100) effects on hematopoietic

G protein-coupled receptors (GPCRs) transmit extracellular signals to the inside by activation of intracellular effector proteins. Different agonists can promote differential receptor-induced signaling responses - termed bias - potentially by eliciting different levels of recruitment of effector proteins. As activation and recruitment of effector proteins might influence each other, thorough analysis of bias is difficult. Here, we compared the efficacy of seven agonists to induce G protein, G protein-coupled receptor kinase 2 (GRK2), as well as arrestin3 binding to the muscarinic acetylcholine receptor M3 by utilizing FRET-based assays. In order to avoid interference between these interactions, we studied GRK2 binding in the presence of inhibitors of Gi and Gq proteins and analyzed arrestin3 binding to prestimulated M3 receptors to avoid differences in receptor phosphorylation influencing arrestin recruitment. We measured substantial differences in the agonist efficacies to induce M3R-arrestin3 versus M3R-GRK2 interaction. However, the rank order of the agonists for G protein- and GRK2-M3R interaction was the same, suggesting that G protein and GRK2 binding to M3R requires similar receptor conformations, whereas requirements for arrestin3 binding to M3R are distinct. Read full article

Expectations, EPS Lags “As Precision Medicine is critical, we cannot think about one size fits all” Dr Pina Cardarelli, Chief Scientific Officer, GPCR Therapeutics Trevena to Participate in Three Upcoming Conferences

Industry News Josephine (Pina) Cardarelli from GPCR Therapeutics on Beyond Biotech Podcast Crinetics

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.; Attwood, M. M.; Rask-Andersen, M.; Schiöth, H. B.; Gloriam, D. E. K.; Liu, H.; Koehler, M.; Zhang, C.; Fan, H.; Alsteens, D. M.; Sotelo, E.; Abal, M. S.; Majellaro, M.; Sotelo, E.; Navarro, G.; Franco, R. V.; Koenekoop, L.; González, A.; Gioé-Gallo, C.; Mallo-Abreu, A.; Brea, J.; Loza, M.

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M., Marti-Solano, M., Sandhu, M., Kobilka, B. K., Bouvier, M., & Babu, M. M. (2023). Howard, M. K., Hoppe, N., Huang, X. P., Macdonald, C. B., Mehrota, E., Grimes, P.

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M., Medel-Lacruz, B., Baidya, M., Makarova, M., Mistry, R., Goulding, J., Drube, J., Hoffmann, C., Owen M., Shukla, A. K., Selent, J., Hill, S. J., & Calebiro, D. (2023). M., Kawakami, K., Masureel, M., Maeda, S., Garcia, K. C., von Zastrow, M., Inoue, A., & Kobilka, B. I., & von Zastrow, M. (2001).

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M. (2011). Deep mutational scanning: assessing protein function on a massive scale. M., Stephany, J. J., & Fields, S. (2014). Nature Protocols , 9 (9), 2267–2284. https://doi.org/10.1038/nprot.2014.153 Howard, M. M., Trinidad, D. D., English, J. G., Coyote-Maestas, W., & Aashish Manglik. (2024). BioRxiv (Cold Spring Harbor Laboratory) . https://doi.org/10.1101/2024.04.17.590000 Pines, G., Fankhauser

A recent breakthrough study published in Nature by Makaía M. Papasergi-Scott, M. M. et al. Time-resolved cryo-EM of G-protein activation by a GPCR.

K., Odongo, S., Radwanska, M., & Magez, S. (2023). M., Thian, F. S., Kobilka, T. S., Schnapp, A., Konetzki, I., Sunahara, R. K., Gellman, S. M., Manglik, A., Hu, J., Hu, K., Eitel, K., Hübner, H., Pardon, E., Valant, C., Sexton, P. M., Christopoulos, A., Felder, C. C., Gmeiner, P., Steyaert, J., Weis, W. I., Garcia, K. M., Dukkipati, A., Feinberg, E. N., Angelini, A., Waghray, D., Dror, R. O., Ploegh, H.

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50% displacement threshold and progressed to seven-point concentration–response assays (10⁻¹⁰ to 10⁻⁶ M) Table reporting the % of displacement measured at 1 µ M and the corresponding Ki for those showing a Hoechst-stained nuclei (blue) across increasing concentrations of AAN396, AAN397 and AAN405 (10⁻¹⁰ to 10⁻⁶ M)

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The fission yeast Schizosaccharomyces pombe has two mating types, Plus (P) and Minus (M). investigated the stringency of the two GPCRs, Mam2 and Map3, for their respective pheromones, P-factor and M-factor acid residues of Map3, F214 and F215, are key residues important for discrimination of closely related M-factors

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M. et al. 2018; Manglik, A. et al. 2012). the formation of dimers and alter their function by destroying the interface between two receptors (M. structure of CB1R–5HT2AR heterodimers, preventing cognitive impairment while preserving analgesia in vivo (M.

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Franziska M Heydenreich, Michel Bouvier, Brian Kobilka, M Madan Babu, and their team's work on Molecular

David Reiner-Link , Alessandro Berghella , Brinda K Rana , G Enrico Rovati , Valerie Capra , Caroline M Abigail Alwin , Campbell Krusemark , Ezequiel Marron Fernandez de Velasco , Steven H Olson , Lauren M

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