For drug hunters working at the GPCR interface, the difference between a successful lead and a dead-end Better Predictions For drug discovery scientists, time and predictive accuracy are the currency of success pipeline translates directly into better prioritization, cleaner data packages, and fewer late-stage surprises Unlock Assay Volume Control Only in Terry’s Corner 🎬 Watch Course Trailers Not sure yet? Subscribe to The Kenakin Brief  today ➤

Breakthroughs this week: New work clarifies how active-state GPCR conformations can support coupling GPCR internalization and soluble proteins; core meetings from GPCR Forum to Biophysics; plus targeted summits That subtle distinction opened the door to a brand-new assay format. For GPCRs, fluorescent ligands have quietly become one of the most versatile technologies—supporting Subtype specificity:  selectively track receptor subtypes in complex brain tissue.

This makes it an ideal candidate for GPCR research, where accuracy in detecting subtle signaling changes

blood-brain-barrier (BBB) and the complexity of the central nervous system (CNS) pose a challenge for developing successful central role in neuronal signaling and have been used to treat these diseases with varying degrees of success One of the biggest hurdles is the understanding and correct targeting of the different receptor subtypes promotes nucleotide release from, and activation of, the G protein α-subunit. Greater specificity : allows for selective tracking of receptor subtypes in complex brain tissues.

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Ignore these forces, and your “selective” agonist may deliver surprises the first time it meets a patient Surface vs. This section raises a critical design question for teams Are you sure your “antagonist” is enough—or Subscribe today and get direct access to decades of pharmacology experience that turn complex systems Subscribe to The Kenakin Brief today ➤

GPCR Reagent Portfolio pHSense™ is the latest addition to Revvity’s GPCR reagent portfolio , which supports Its GPCR research tools  support discovery teams and academic labs with precision reagents and validated

occupancy and complex activity, leverage hemi-equilibrium calcium assays, recognize fractal potency, and surface Corner members get to rewatch the recording Subscribe to the Kenakin Brief and Join the Live AMA ➤ Celtarys nanodiscs, peptidiscs, SMALPs, SPR, ITC—plus how construct design and solubilization choices shape success need to brief leadership, plan experiments, or time a move in the market or your career, Premium makes sure 🗞️ Weekly research, careers & event intelligence 🤝 Members-only networking, AMAs & matchmaking 💡 Support

Onset and offset rates (not just “final numbers”) decide which drugs succeed in patients and which ones Suddenly, at higher doses, you see an exaggerated ‘bang’ of effect. It’s like waiting for popcorn: at first, nothing happens, then suddenly the bag explodes with pops. them Exclusive access  to the next AMA session Direct engagement opportunities  through AMAs and topic suggestions Subscribe to The Kenakin Brief  today ➤

Upcoming events:  “Drug Discovery at Superluminal Speeds”; and Discovery on Target 2025—GPCR track you Engineer assays on purpose:  Set ranges, controls, and system sensitivity to surface mechanism—before Also super-valuable for those of us learning how to teach pharmacology." — DrGPCR University Attendee

Flow cytometry, a laser-based method, is used to examine single cells suspended in a fluid. Autofluorescence and multiplexing: Using far-red or near-infrared fluorophores can reduce background and support At Celtarys, we support this transition by offering optimized fluorescent ligands specifically designed CELT-240 in flow cytometry binding assays is suitable to measure the affinity of compounds for the D2

Suddenly, your snapshot becomes a forecast . The question was: could crude gp120 supernatant be used instead, without corrupting results? Chemists suddenly have meaningful levers to pull. The lesson: models don’t just need data. Subscriber-driven topics,  so the next lesson addresses your bottleneck. Subscribe to The Kenakin Brief today ➤

Superluminal Medicines: AI/ML Meets GPCR Pharmacology As Ajay continued to explore how GPCR signaling To address this, he co-founded Superluminal Medicines , a biotech company focused on integrating machine Superluminal is building systems that learn from receptor movement, conformational shifts, and complex In August 2025, Superluminal Medicines announced a collaboration with Eli Lilly and Company to advance Takeaway: Ajay Yekkirala’s story is not just about GPCR science or startup success.

insights for drug discovery Hi GPCR Friends, Every week, critical decisions in GPCR research hinge on subtle underpowered studies, this module hands you a practical framework to validate differences, confirm subtle Eliminate subjective calls:  From t-tests to ANOVA and F-tests, know which tool to apply when, so debates This is where the real conversations begin—made possible with the support of NIS, Proteos, and Axxam  

SNAP-tag has been successfully used while preserving activity. It can even study the GPCR distribution within endocytic vesicles and across subcellular compartments Cell-surface protein-protein interaction analysis with time-resolved FRET and snap-tag technologies:

Our Sponsors This event would not be possible without the generous support of our sponsors: NIS Proteos Axxam Axxam is a leading provider of integrated discovery services, supporting the entire drug discovery This comprehensive approach enables Axxam to support clients worldwide in identifying and optimizing

And when decisions ride on subtle shifts, “looks different” isn’t good enough. Subtle shifts vanish in noise. them Exclusive access to the next AMA session Direct engagement opportunities  through AMAs and topic suggestions Subscribe to The Kenakin Brief today ➤ #ttest #ANOVA #poweranalysis #curvecomparison #ftest #assayvalidation

There, she chose to write a review on genetic variation in susceptibility to alcoholism and opioid addiction—a I was staying up super late. I was excited to work on this, till 2 or 3 a.m.” Her current work examines how these substances, when used alone or together, impair breathing in mice This mindset can lead to a more fulfilling and successful career.

While writing a literature review on opioid and alcohol addiction susceptibility, something shifted. Lessons from Catherine’s Story Catherine’s career challenges the idea that success requires a straight 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.

Blueprint for survival:  Continuous improvement and operational scaffolding—not more hires—are the real

These results support the use of fluorescence-based screening methods as a reliable alternative to classical

Her findings highlight how fentanyl suppresses inhalation while xylazine prolongs exhalation, creating than medicine can adapt, Catherine’s work shows why overdose research must evolve alongside the drug supply That surge mirrors what’s happening nationally. The insight is simple but urgent: the drug supply evolves faster than medicine.   And the illicit supply is moving faster than clinical medicine can adjust.

When a PAM increases radioligand binding but suppresses functional response, it’s not broken pharmacology—it Suddenly, the agonist works . Terry Kenakin An always-growing library of on-demand pharmacology insights The ability to vote on or suggest Subscribe to The Kenakin Brief today ➤ #AllostericPharmacology #GPCR #BindingVsFunction #ReceptorPharmacology

On the other hand, fluorescent ligands have a superior safety and environmental profile.

Moore, was most definitely a success. Now back in Europe, all she can think about is next year’s date, in Dublin, where she is sure she will

CELT-335 was successfully used in assays to determine the pharmacological properties of Δ9-tetrahydrocannabinol When this happens the proximity between donor and acceptor is sufficient for a transmission of energy

New scaffolds modulating the CBRs in both the orthosteric and allosteric sites have been developed, supported of the series developed by Pfizer, including CP5594, gave rise to a new class of abused psychoactive substances GPCRs are not suitable for antibody use due to steric hindrance and reverse binding, thus, other strategies Among them, we have chosen the SNAP-tag, a suicide enzyme technology. Cell-Surface Protein-Protein Interaction Analysis with Time-Resolved FRET and Snap-Tag Technologies:

the minimal chemical modifications in the original ligand, high sensitivity and their extensive and successful (3H) labeled ligands are usually chemically identical to the original, because tritium will usually substitute and more accessible alternative. -            Quantitative cell binding studies : Radioligands have superior

Introduction Dopamine receptors are G-protein-coupled receptors (GPCRs), which have 5 subtypes -D1-5. The estimated Z’ of the assay is 0.71, which is sufficient for HTS standards. Figure 3.   No substantial differences were found between them and the reporter. Figure 4.     These results indicate that CELT-419 is suitable for live-cell assay with automated microscopy. Evaluation of Fluorophores for Optimal Performance in Localization-Based Super-Resolution Imaging.

O-acylisourea rearranging intramolecularly into the N-acylurea.[ 2]     NHS ester amide coupling  is the most suited This property comes from the wide chemical space this reaction can access – we can substitute one reagent Semiquantitative Study of the EDC/NHS Activation of Acid Terminal Groups at Modified Porous Silicon Surfaces Chapter Three - Bioconjugated Materials in the Development of Subunit Vaccines.