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site and a GPCR Paper with his team: Targeted Drug Design through GPCR Mutagenesis: Insights from β2AR China M Payne ,   Cam Sinh Lu ,   Karen Gregory ,  Lauren May ,  Andrea Vernall , et al. for their fantastic

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

February 2022 Trevena Announces Submission of New Drug Application in China for OLINVYK® by its Partner by data from a Phase 3 bridging study of oliceridine injection compared to IV morphine, conducted in China success payments upon approval and commercialization milestones, as well as a 10% royalty on net sales in China commercialization of novel medicines for patients with central nervous system (CNS) disorders, today announced that China United States by the Food and Drug Administration (FDA) for use in adults for the management of acute pain

CXCR4 takes on a nuclear role in red blood cell maturation CXCL13/CXCR5 emerges as a high-potential pain target ST171, a biased 5‑HT1A agonist, delivers selective pain relief in preclinical models Dr.GPCR Blocking this chemokine axis reduces pain  hypersensitivity by dampening neuroinflammation and glial This novel agonist activates Gi/o selectively , avoiding β-arrestin and showing strong pain relief in

Watch Episode 170 Thinking Differently Pain research has long followed a familiar route: from molecule conventional bottom-up approach often fails to deliver therapies that truly help patients, especially in the pain patient-centric and behavior-first approach uncovered robust gene expression signatures  linked to pain Why This Approach Matters In pain research, bottom-up approaches often fail to translate. Alex Serafini makes the case for building pain research from the clinic down, not the bench up. _____

Watch Episode 170 What We’re Missing in Pain Research In GPCR drug discovery, receptors typically steal Signaling (RGS proteins)  might hold some of the most untapped therapeutic opportunities, particularly in pain Venetia Zachariou  introduced him to the power of RGS proteins — particularly RGS4  — in modulating pain models and hints that RGS proteins could modulate pain chronification itself . Serafini highlighted that in modern pain drug development, the field has remained too focused on ion

After years of living with unresolved pain following surgery for a pilonidal cyst, Alex was left without This is a story about how chronic pain doesn't just shape lives — it reshapes careers. “I wasn’t able to get stronger pain meds,” he said. “So I had to understand the biology myself.” Mike Caterina on pain mechanisms in the peripheral nervous system. , pain neuroscience

Company’s novel S1P1 receptor modulator being developed as a potential treatment for diabetic neuropathic pain

November 22, 2021 JUPITER, FL—Scientists at Scripps Research in Florida have created a collection of new pain-relieving

of curiosity, persistence, and using science to meet unmet clinical needs, especially in the chronic pain Clifford Woolf, a leader in pain biology. slow down or prevent good science from reaching patients — particularly in underfunded fields like pain seeds for what would later become Blue Therapeutics, a startup he co-founded to develop non-addictive pain Whether it's chronic pain, addiction, or another unmet need, keeping the real-world impact in focus can

M.; Compton, D. R.; Martin, B. R.; Abood, M. E. , M. C.; Westphal, M. V.; Mostinski, Y.; Mach, L.; Wasinska-Kalwa, M.; Weise, M.; Hoare, B. .; Maccarrone, M.; Veprintsev, D. B.; Carreira, E. M.; Grether, U.; Nazaré, M. F.; Nicolotti, O.; Perrone, M. G.; Brea, J.; Loza, M. I.; Infantino, V.; Abate, C.; Contino, M.

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M., & Fields, S. (2014). Deep mutational scanning: a new style of protein science. M., Marti-Solano, M., Sandhu, M., Kobilka, B. K., Bouvier, M., & Babu, M. M. (2023). Kosar, M., Sarott, R. C., Sykes, D. A., Viray, A. E., Vitale, R. M., Tomašević, N., ... & Carreira, E. M. (2024). M., Christopoulos, A., & May, L. T. (2016).

a variety of potential clinical applications with a great interest in the treatment of neuropathic pain optimization, this series of compounds could represent potential clinically useful S1R ligands for pain

John Streicher talks about his work on terpenes found in cannabis as these may be a novel way to treat pain These compounds may be a novel way to treat pain without the negative side effects of cannabinoids or

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.

Therapeutics Doses First Subjects In Phase 1 Clinical Trial Of CFTX-1554 For The Treatment Of Neuropathic Pain CFTX-1554 is being developed as a non-opioid approach to the treatment of neuropathic pain, a debilitating

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The activation of these pathways regulates pain modulation, memory consolidation, motor coordination neuroprotective functions and is now being investigated for its role in Parkinson’s disease and neuropathic pain Biomed Pharmacother. 2018 Feb;98:222-232. doi: 10.1016/j.biopha.2017.12.056 Azam S, Haque ME, Jakaria M, ):11646-11664. doi: 10.3390/cimb46100691   Navarro G, Sotelo E, Raïch I, Loza MI, Brea J, Majellaro M.

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).

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.

receptor type 2 (CB2R) has emerged as a compelling target across inflammation, immune modulation, and pain 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)

References Barbazán J, Majellaro M, Martínez AL, Brea JM, Sotelo E, Abal M. Soave M, Briddon SJ, Hill SJ, Stoddart LA.

References Fessl T, Majellaro M, Bondar A. Navarro G, Sotelo E, Raïch I, Loza MI, Brea J, Majellaro M.

M. Aragay et al. 1998). Removal of G proteins by using CRISPR KO of Gαi (Gαi KO) or KO of all Gα subtypes (Gα_all KO) (M. constitutively internalize through clathrin-coated pits independently of phosphorylation and β-arrestin (M. M. Paing et al. 2022; J. L. Sapmaz et al. 2019, M. N. J. Seaman 2012).

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