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Zhan-Guo Gao, Mansour Haddad, and Kenneth A Jacobson for their work on A2B adenosine receptor signaling

Terry’s Corner: Why Binding Kinetics Matter More Than Affinity In drug discovery today, time wasted is interpret kinetic binding experiments and recognize when a drug’s rate of onset and offset matter more than

I’m honored to be chairing a session  in this track — with none other than Terry Kenakin  on the speaker Hearing Terry speak is more than an academic experience — it’s like being handed a new set of tools to

Exploring the kinetic factors that enhance in vivo efficacy beyond traditional potency metrics, as presented by Dr. GPCR. Hey GPCR Fans, This week's breakthroughs are crucial for staying ahead in the rapidly evolving landscape of GPCR research and drug discovery. Dr. Terry Kenakin's insights on target residence time can reshape how you evaluate and advance lead compounds, potentially saving your team from costly late-stage failures. That's exactly what Dr. GPCR delivers every week: practical tools and critical intelligence to elevate your science and sharpen your decisions. Breakthroughs this week: Novo Nordisk cuts Ozempic® cost; Nxera launches obesity pipeline; Superluminal–Lilly cardiometabolic partnership; New GPCR allosteric sites; GPCR signaling potentiation by ATP and sugars. 🔍 This Week in Dr. GPCR Premium: Sneak Peek Get a glimpse of the in-depth intelligence available exclusively to our Premium Members this week: Industry insights:  Discover the latest strategic moves in the pharmaceutical sector, from new pipelines targeting obesity to significant collaborations in cardiometabolic disease, and gain insights into novel approaches in neurodegeneration and antibody therapeutics. Upcoming events:  Stay informed about key global conferences and symposia focusing on GPCRs, neuropharmacology, drug discovery, and biophysics, ensuring you don't miss crucial networking and learning opportunities. Career opportunities:  Explore a selection of high-level job openings in high-throughput screening, research, biologics development, clinical operations, and biostatistics within leading organizations. Must-read publications:  Stay updated on cutting-edge research, including the potentiation of GPCR signaling by ATP and sugar monophosphates and the identification of a novel allosteric site on the vasopressin V2 receptor. Terry's Corner - Unlock the Power of Target Residence Time in Your GPCR Drug Discovery Pipeline Gain a critical edge by understanding the in vivo efficacy drivers overlooked by traditional potency metrics. Are your promising in vitro results failing to translate into real-world clinical success? Dr. Terry Kenakin’s latest insights delve into target residence time, revealing why kinetic persistence often trumps binding affinity for in vivo efficacy. Discover how factors like restricted tissue diffusion and receptor density can dramatically alter drug action, potentially unlocking the true potential of your lead compounds. Problem Solved:  Eliminate the blind spots in your drug evaluation process, moving beyond simple potency measures to understand the dynamic interactions that govern in vivo effectiveness. Competitive Edge:  Identify high-value compounds that might be missed by traditional screening methods, gaining a first-mover advantage in developing more effective therapeutics. Threat Avoided:  Prevent costly late-stage failures by incorporating kinetic modeling early in your pipeline, ensuring your candidates have the persistence needed for clinical impact. ➡️  Premium Members get 50%+ discount when they join Terry’s Corner. Access this week’s key insight ➤ Dr GPCR Podcast – Decoding the Deadly Duo: Xylazine, Fentanyl, and Respiratory Depression Understand the synergistic mechanisms driving the escalating opioid crisis and the crucial role of GPCR pharmacology. The opioid crisis is evolving with the dangerous combination of fentanyl and the veterinary sedative xylazine. This week’s featured podcast episode with Catherine Demery explores the distinct yet lethal mechanisms by which these drugs impair respiration. Learn how fentanyl slows inhalation via opioid receptors, while xylazine prolongs exhalation through alpha-2 adrenergic receptors, creating a synergistic effect that drives overdose deaths. Catherine’s research, blending GPCR signaling studies with public health data, offers critical insights into this urgent crisis. Problem Solved:  Gain a deeper understanding of the pharmacological underpinnings of opioid overdose, informing the development of more effective intervention strategies. Competitive Edge:  Stay informed on emerging public health threats and the scientific research aimed at addressing them, positioning your work at the forefront of critical biomedical challenges. Threat Avoided:  Recognize the growing prevalence and dangers of xylazine-laced opioids, enabling you to contribute to solutions and understand the broader impact on public health. Listen now to understand how two mechanisms intersect—and why pharmacologists are critical in addressing this crisis ➤ Call for Papers – GPCRs: Signal Transduction Volume II With over 21,000 views  and 7,785 downloads  from Volume I, the Signal Transduction  Research Topic is back. Volume II invites experts to deepen our collective understanding of GPCR pathways in health and disease. Manuscript summary deadline: 24 September 2025 . Final submissions: 12 January 2026 . Why contribute: Join a global, like-minded GPCR community. Shape the next generation of cellular biochemistry research. Amplify your work with high-impact visibility. Submit your paper today to secure your work in Volume II ➤ Why Dr. GPCR Premium Membership Gives You an Edge Every week, Premium delivers noise-free intelligence : expert-led courses, classified industry insights, curated events, exclusive job opportunities, and insider commentary. Designed for GPCR scientists and translational teams, Premium keeps you informed on the science, careers, and business moves shaping drug discovery. Unlike fragmented feeds and endless searches, Premium is structured to help you move faster, smarter, and with greater clarity. FAQ: Premium Membership 🔹 What’s included? The complete Weekly News digest, curated jobs, upcoming events, classified GPCR publications, exclusive on-demand expert lectures, and member-only discounts. 🔹 Who is it for? GPCR scientists, translational pharmacologists, biotech discovery teams, and decision-makers who need career-relevant intelligence to stay ahead. 🔹 Why now? 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GPCR Summit 2022 is less than a month away!

August 2022 "Opioid receptors (ORs) represent one of the most significant groups of G-protein coupled receptor (GPCR) drug targets and also act as prototypical models for GPCR function. In a constant effort to develop drugs with less side effects, and tools to explore the ORs nature and function, various (poly)pharmacological ligand design approaches have been performed. That is, besides classical ligands, a great number of bivalent ligands (i. e. aiming on two distinct OR subtypes), univalent heteromer-selective ligands and bitopic and allosteric ligands have been synthesized for the ORs. The scope of our review is to present the most important of the aforementioned ligands, highlight their properties and exhibit the current state-of-the-art pallet of promising drug candidates or useful molecular tools for the ORs." Read more at the source #DrGPCR #GPCR #IndustryNews

Guo, W., et al., Crosstalk in G protein-coupled receptors: Changes at the transmembrane homodimer interface

each G protein with the receptor showed that there are more polar interactions in Gq/Gs engagements than , Z., Liu, C., Li, X., Zhu, X., Wang, N., Xu, Z., Xia, R., Liang, J., Duan, Y., Yin, H., Xiong, Y., Zhang , A., Guo, C., Chen, Z., Huang, Z., & He, Y. (2022).

M., Pérez-Hernández, G., Batebi, H., Gao, Y., Eskici, G., Seven, A.

Carlsson, J., Yoo, L., Gao, Z. G., Irwin, J. J., Shoichet, B. K., & Jacobson, K. A. (2010).

coupling was primarily attributed to differences in the conformational dynamics of the receptor rather than Sun D, Gao W, Hu H, Zhou S. Why 90% of clinical drug development fails and how to improve it? Lu S, He X, Ni D, Zhang J. Shen S, Zhao C, Wu C, Sun S, Li Z, Yan W, et al. González-Maeso J, Weisstaub NV, Zhou M, Chan P, Ivic L, Ang R, et al.

N-termini that mediate ligand binding and signaling (Bannert N et al. 2001; Casarosa P et al. 2005; Gao

Research FP assays work on the principle that a fluorescent ligand bound to protein rotates slower than Adapted from: Zhang Y, Tang H, Chen W, Zhang J. This makes them very useful for GPCR drug discovery, since receptors are a lot bigger than their small They are more accessible than radioligand assays, since they do not require complex equipment for analysis

This Chemistry Tools session was more industry focused than those before, and Maria shared the floor Xiaoyu Zhang showed great insight into new ligands for new E3 ligases for PROTAC development.

With street-level contamination rising faster than medicine can adapt, Catherine’s work shows why overdose A Crisis That’s Redefining Overdose In 2023, more than 107,000 Americans died from drug overdoses , the The insight is simple but urgent: the drug supply evolves faster than medicine.   The Urgency Ahead Every overdose today is more complicated than the last. And the illicit supply is moving faster than clinical medicine can adjust.

Her story is about more than experiments or data points. Rather than treating opioid pharmacology as a purely theoretical exercise, she collaborates with harm-reduction Academic success is less about prestige than about impact. That urgency, more than titles, positions, or prestige, is what sustains a lasting career in science. Catherine’s story shows that when purpose drives research, science becomes more than a job—it becomes

Rather than carving out turf, they grew by designing around collective capacity . environment lowers friction between these specialties, making innovation structurally inevitable rather than The structure you train in often matters more than the experiment you start with. Weekly seminars were mandatory but lightweight, designed to connect  rather than perform.

Watch Episode 171 Mentoring in science is more than supervising—it’s about shaping the next generation Mistakes are part of learning—and guiding students through them is more valuable than doing everything

“JB” Broichhagen trained as a synthetic chemist — someone who trusted carbon–carbon bonds far more than This was more than data. It was ignition. What emerged was more than a ligand — it was a tool that enabled reproducible, stable, and high-contrast The trust between chemistry and biology drove the project forward faster than either discipline could

development... seeing if we can bring preclinical models much closer to the actual human experience than Rather than starting with a molecular hypothesis, Serafini’s team noticed that hamsters infected with

With the right lens, you’ll see why efficacy is more than signal strength: it's a fingerprint of conformational

Earlier than many teams do. Modern real-time assays can deliver these insights earlier, faster, and cheaper than most teams assume It’s less bureaucratic than most outsiders think. Why kinetic profiling matters more than most teams realize.

despite these targets falling short clinically: “The downstream cascade is probably a little bit weaker than hitting a GPCR... and honestly, like with the trials, they were not really that sufficiently better than

Indeed, the difference is lower than 1pKi value between both experiments. W.; Wu, Y.; Zhao, S.; Shui, W.; Li, S.; Korde, A.; Laprairie, R. B.; Stahl, E. L.; Ho, J. .; Zhao, Q.; Hanson, M. A.; Bohn, L. M.; Makriyannis, A.; Stevens, R. C.; Liu, Z.-J. -H.; Wu, Y.; Wu, L.; Popov, P.; Benchama, O.; Zvonok, N.; Locke, K.; Qu, L.; Han, G. W.; Iyer, M. J.; Wang, J.; Wu, M.; Katritch, V.; Zhao, S.; Kunos, G.; Bohn, L. M.; Makriyannis, A.; Stevens, R.

Less than ~15% of higher plant species, <5% of bacterial and fungal species, and only a fraction of marine This was more than trial-and-error. It was early structure-based pharmacology. Dr. expands drug matter beyond the familiar and encourages deliberate exploration of chemical novelty, rather than

unique ability to combine storytelling, real-world experience, and scientific clarity makes this more than

chemist who would eventually help his lab visualize receptors in living systems with far more precision than The knockout behaved differently than expected. And when those pieces come together, the field jumps forward faster than any lab could push it alone.

The donors used in this technique have longer half-lives  than other fluorophores (between 300μs–1 ms Terbium, a second-generation donor, is brighter than Europium (10-20 times), which increases sensitivity The donor lanthanum fluorophores are more stable than regular fluorophores and quite resistant to photobleaching

article GPCR Publication Highlights βCGRP breaks the mold: Distinct signaling patterns reveal it’s more than

.” — Tom Sakmar This makes them more than biomarkers — they’re potential drivers of disease .