When Sokhom joined Alkermes, the company had a strong development arm, but a relatively underdeveloped tasked with building an in vitro pharmacology group from scratch , including infrastructure, hiring, assay development, and team dynamics.

affinity experiments  are interpreted—and how those interpretations quietly shape SAR, lead selection, and development By walking through saturation curves, displacement assays, stoichiometry pitfalls, and kinetic traps, experiments that tell the truth , ensuring affinity data support—rather than undermine—lead selection and development Research , leaders from academia and biotech unpack what effective collaboration really looks like when developing event alerts, and career-relevant opportunities—organized to support real decisions in discovery and development

cancers, particularly in combination with other immune checkpoint inhibitors.1 In a shared effort to develop A new NanoBRET® competitive binding assay 2  was developed in collaboration with Professor Kevin Pfleger Pfleger’s group in developing assays, led to two new A 2A AR tracers (CELT-463 and CELT-464) , bearing First, saturation binding assays were performed . E. 1-Alkyl-8-(Piperazine-1-Sulfonyl)Phenylxanthines: Development and Characterization of Adenosine A2B

Functional assays can suggest clarity while quietly masking complexity, creating the illusion of competitive Each experimental decision — system sensitivity, assay configuration, kinetic design — carries strategic Assay Sensitivity and System Configuration Receptor expression level is a strategic variable. Best Habits for Data Quality and Reproducibility Detection assays identify activity; they do not validate promising hits into mechanistic evaluation quickly Use statistics to arbitrate interpretation Design assays

thrilled to have entered a strategic partnership with Eurofins DiscoverX , a global provider of GPCR assay This partnership connects advanced assay and biology capabilities with the scientists and organizations Why this deserves attention: Assay breadth matters.  Platform selection shapes interpretation. Weekly News  — Curated industry developments, classified publications, and signal-focused intelligence Scientists living and working in developing countries can join for $25 per year — permanently set to

visibility and adoption of Celtarys’ cutting-edge fluorescent ligand technology and accelerate the development Celtarys Research develops high-quality, fluorescently labeled ligands and innovative chemical biology tools to support real-time, non-radioactive GPCR assays. About Celtarys Research Celtarys Research is a biotech company based in Spain that specializes in the development development, screening, and live-cell imaging.

In this session, you’ll gain: Why saturation and displacement assays fail when protein stoichiometry The midpoint and maximum—core parameters for downstream modeling—are only meaningful when the assay fully Displacement Curves and the Illusion of Potency Displacement assays measure affinity when no traceable Equilibration time:  Many assays stop before the system reaches equilibrium, especially with slow competitors

Someone with strong assay development skills as well as strong data analysis and interpretation skills Mark:  “Are there particular assay types of interest?” Beth:  “We focus on biochemical, cell based, and radioligand binding assays to enable SAR, MOA, lead s comradery and open exchange in our team and I strive to provide learning opportunities for career development

Must-read publications: D2 receptor constitutively active mutants; β2AR allosteric SERS assay; CXCR4 Start learning here ➤ Terry’s Corner — Early Safety Assays For Better GPCR Drug Discovery Decisions Too Terry Kenakin walks through the core early assays that protect your chemistry, budget, and timeline. Each week, you receive curated, signal-focused intelligence: industry developments, classified publications

when tested in orthogonal functional assays. Without multi-pathway assays, selectivity assessments can be misleading. cognition, and addiction but also produce serious dysphoria, which has historically precluded clinical development tools developed by Professor Terry Kenakin at the University of North Carolina School of Medicine for Drug Discovery and Development’ eBook and ‘GPCR Functional Cell-based Assays – Assessing Biased Signaling

Traditional assays—particularly membrane-based radioligand binding—often provide high-throughput measurements study, 16 synthetic cannabinoid receptor agonists (SCRAs) were evaluated using a CB2 live-cell HCS assay Traditional membrane-based assays isolate receptors from this environment, which simplifies quantification Visual displacement provides an additional confidence layer that traditional homogeneous binding assays or GPCR-mediated analgesia, these findings reinforce the value of physiologically relevant binding assays

When assays behave unpredictably, the wrong interpretation doesn’t just waste time; it costs viable compounds , credibility, and millions in development risk. Career opportunities:  Postdocs in GPCR biophysics and assay development; industry scientist roles at Protect your pipeline:  Misinterpreting displacement curves in allosteric assays means discarding viable Aside from his vast experience in drug development, not to mention his extensive publication record,

GPCR Assay Strategy: Why Binding Studies Alone Miss Biased Signaling Binding assays remain useful as The appropriate response is a multi-assay strategy. Eurofins DiscoverX has developed an extensive platform of GPCR functional assays — including β -arrestin Terry Kenakin, read the complete article on the Eurofins DiscoverX page: GPCR Drug Discovery and Development Related Resources eBook: Insights into GPCR Drug Discovery and Development: Exploring GPCR-Ligand Interactions

Patient derived iPSC's, organoid systems, and biosensor-based assays introduce models that better preserve cover how patient-derived induced pluripotent stem cells (iPSCs), organoid systems, and biosensor-based assays signaling, producing a fundamentally different pharmacological pattern — with different consequences for assay Discovery Summit brings together scientists working at the intersection of GPCR biology and therapeutic development

Leveraging decades of experience, their services include AI-driven target identification, target validation, assay development, compound management, and high-throughput screening in both 384- and 1536-well formats. platform, iPSC-derived models, optogenetics, and high-content screening techniques such as cell painting assays

This conjugation is very useful for tagging biomolecules and can also be used to develop fluorescent Chapter Three - Bioconjugated Materials in the Development of Subunit Vaccines.

the biological environments they aim to represent. iPSC-derived cells, organoids, and biosensor-based assays pluripotent stem cells (iPSCs), iPSC-derived cardiomyocytes, organoid systems, and biosensor-based assays Discovery → Read DiscoverX article A2A Fluorescent Competitive Binding with NanoBRET® → Explore assay development, orthosteric/allosteric mechanisms, and kinetic modeling. Aside from his vast experience in drug development, not to mention his extensive publication record,

blood-brain-barrier (BBB) and the complexity of the central nervous system (CNS) pose a challenge for developing Both orphan and well-characterized GPCRs are untapped opportunities for drug development targeting CNS Faster assay development: also speeds GPCR target validation. concerns and regulatory hurdles: Non-radioactive alternative to screening In the context of CNS drug development A Robust and Efficient FRET-Based Assay for Cannabinoid Receptor Ligands Discovery.

pharmacologists misinterpret how an antagonist interacts with its receptor, the consequences ripple across assay development, SAR interpretation, and clinical translation.

GPCR Binders, Drugs, and more Development of a 5-HT7 receptor antibody for the rat: the good, the bad Industry News Data Presented at AACR 2023 Highlights Exscientia’s Clinical and Preclinical Development Progressive Technologies and Approaches Revealing Novel GPCR Biology and Drug Development Potential. FREE Symposium - IPI Surfacing (June 15, 2023) Training School on “Cell-based assays to study Adhesion Development Post Doctoral Fellow Research associate in protein production Vice President, Oncology Clinical

ligand mechanism to the decisions that shape affinity, efficacy, selectivity, safety, and downstream assays That subtle distinction opened the door to a brand-new assay format. Instead of imaging-heavy workflows, pHSense offers a no-wash, plate-reader–ready, high-throughput assay Cleaner data:  higher signal-to-noise ratios sharpen CNS assays. Speed:  faster GPCR target validation and assay development.

Progressive Technologies and Approaches Revealing Novel GPCR Biology and Drug Development Potential. FREE Symposium - IPI Surfacing (June 15, 2023) Training School on “Cell-based assays to study Adhesion - Antibody Engineering Scientist—Immuno-Oncology Convergent Research - Senior Scientist, Cell-Based Assay Development Explore Dr.

GPR37L1 controls maturation and organization of cortical astrocytes during development. Progressive Technologies and Approaches Revealing Novel GPCR Biology and Drug Development Potential. FREE Symposium - IPI Surfacing (June 15, 2023) Training School on “Cell-based assays to study Adhesion IRN I-GPCRNet (October 25 - 27, 2023) GPCR Jobs Convergent Research - Senior Scientist, Cell-Based Assay Development Post Doctoral Fellow Research associate in protein production Vice President, Oncology Clinical

Methods & Updates in GPCR Research NanoBiT- and NanoBiT/BRET-based assays allow the analysis of binding Progressive Technologies and Approaches Revealing Novel GPCR Biology and Drug Development Potential. FREE Symposium - IPI Surfacing (June 15, 2023) Training School on “Cell-based assays to study Adhesion - Antibody Engineering Scientist—Immuno-Oncology Convergent Research - Senior Scientist, Cell-Based Assay Development Explore Dr.

presented at the 23rd BioEquity Conference British Patient Capital Invests £10m in next-generation drug development Progressive Technologies and Approaches Revealing Novel GPCR Biology and Drug Development Potential. FREE Symposium - IPI Surfacing (June 15, 2023) Training School on “Cell-based assays to study Adhesion - Antibody Engineering Scientist—Immuno-Oncology Convergent Research - Senior Scientist, Cell-Based Assay Development Explore Dr.

Progressive Technologies and Approaches Revealing Novel GPCR Biology and Drug Development Potential. FREE Symposium - IPI Surfacing (June 15, 2023) Training School on “Cell-based assays to study Adhesion Antibody Engineering NEW Scientist—Immuno-Oncology Convergent Research - Senior Scientist, Cell-Based Assay Development Post Doctoral Fellow Research associate in protein production Vice President, Oncology Clinical

October 2022 "We describe production of the human A2A adenosine receptor (A2AAR), a class A G protein-coupled receptor (GPCR) for 19F-NMR and single-molecule fluorescence (SMF) spectroscopy. We explain in detail steps shared between the two sample preparation strategies, including expression and isolation of A2AAR and assembly of A2AAR in lipid nanodiscs and procedures for incorporation of either 19F-NMR or fluorescence probes. Protocols for SMF experiments include sample setup, data acquisition, data processing, and error analysis. For complete details on the use and execution of this protocol, please refer to Wei et al. (2022) and Sušac et al. (2018)." Read more at the source #DrGPCR #GPCR #IndustryNews

Pipeline Efficiency Begins With the Chemistry Itself Drug discovery pipelines often stall not because the target is wrong—but because the chemical matter  interacting with that target lacks the right properties to produce meaningful pharmacology. We obsess over target validation, signaling pathways, expression patterns, and disease relevance. Yet, far less time is spent scrutinizing the structural logic and origin  of the molecules we screen in the first place. This lesson asks a deceptively simple question: What if our molecules—not our targets—are limiting discovery? In this lesson, you’ll gain: A strategic view of how chemical scaffolds shape pharmacologic outcomes An understanding of new chemical sources beyond natural agonist analogs Awareness of how GPCR allostery and biased signaling are redefining drug design The Long Arc of Chemical Pharmacology The early history of drug discovery was rooted in nature . Extracts from plants, fungi, bacteria, and environmental microorganisms provided the first potent modulators of physiology. Opium, for example, was used for dysentery and relief of suffering as early as the 3rd century BC; its derivatives — morphine, codeine, papaverine — became cornerstones of modern therapy.  The natural world still holds enormous untapped potential . Less than ~15% of higher plant species, <5% of bacterial and fungal species, and only a fraction of marine organisms have been meaningfully explored.  Yet natural-product scaffolds come with costs: they are structurally complex, expensive to modify, often unpredictable in IP , and sometimes more difficult to optimize for modern pharmacokinetics.  Still, nature remains a treasure map — just one that requires more strategic navigation. The key question Terry raises: If natural scaffolds provided our starting pharmacology, what new scaffolds will define the next 50 years? Building on Known Pharmacology Medicinal chemists learned early that modifying endogenous molecules — hormones, neurotransmitters, and metabolic signals — could yield new drug effects. Adenine-derived scaffolds enabled selective adenosine receptor antagonists; tryptophan modifications led to somatostatin receptor ligands.  From these efforts emerged the concept of privileged structures : chemical backbones that show repeat utility  across GPCR classes and receptor families. Indoles, benzodiazepines, phenethylamines — each recurs because it “fits” biology well.  This was more than trial-and-error. It was early structure-based pharmacology. Dr. Kenakin highlights how hybrid molecules  — combining two pharmacophores into one scaffold — enable dual-modality treatments with unified pharmacokinetics  (instead of juggling two separate drugs with mismatched ADME profiles).  And occasionally, new chemistry emerges from an unexpected source: Side effects. Diuretic action discovered in sulfanilamide derivatives led to furosemide; sedative effects of early antihistamines helped launch antipsychotics.  Lesson:  The structure-response relationship is rarely linear — and observing the unexpected is part of the craft. Informatics Expands the Search Space for Chemical Drug Matter Advances in chemoinformatics  introduced large-scale similarity mapping, such as SEA (Similarity Ensemble Approach), which compares the chemical similarity of ligands , not the protein sequence of targets.  This is a philosophical shift: Instead of asking, “Which proteins are related?” We ask, “Which molecules behave as if they belong together?” This approach reveals: Hidden target overlap New therapeutic hypotheses “Off-target” effects that may be on-target opportunities This expands drug matter beyond the familiar and encourages deliberate exploration of chemical novelty, rather than incremental tuning of existing scaffolds. The molecule, not the receptor, becomes the guiding principle. Allostery and Biased Signaling Change the Game The most profound change in GPCR drug discovery is our expanding understanding of allosteric receptor function . GPCRs are not simple on/off switches. They are allosteric machines , able to shift conformational states in response to multiple binding influences.  This enables: Positive Allosteric Modulators (PAMs) — enhance natural signaling Negative Allosteric Modulators (NAMs) — attenuate signaling Biased agonists  — favor one intracellular pathway over another These are not analogs of natural transmitters. They are structural strategies for tuning physiology. This reroutes discovery toward: Functionally selective ligands Better therapeutic windows More predictable clinical behavior Allosteric modulation allows us to work with  biology’s dynamic systems instead of forcing orthosteric competition. Biologics Are Now Chemical Drug Matter, Too Proteins, peptides, and antibodies are no longer niche. They are mainstream pharmacology. They offer high specificity , favorable safety , and unique mechanisms , including GPCR modulation through agonism, internalization, or ligand scavenging.  Advances in formulation and delivery have overcome earlier pharmacokinetic limitations. Peptide GPCR therapies now address obesity, diabetes, cancer, neuroendocrine disorders, inflammatory diseases, and more.  The boundary between “small molecule” and “biologic” has blurred. What matters now is not the category , but the fit: Does the chemical matter support the therapeutic mechanism? Does it interact with the receptor in a way that biology can use? Core message: The receptor is only half the story. The molecule is the other half. Why Terry’s Corner Terry’s Corner is a continuously growing knowledge platform built for scientists who want sharper decision-making power in discovery pharmacology. Subscribers gain weekly lectures led by Dr. Terry Kenakin, monthly AMA discussions, and on-demand access to a library of expert GPCR teaching sessions. Members can also propose new topics, ensuring relevance to real-world discovery problems. This is strategic, method-proven insight for discovery teams, pharmacologists refining core skills, and R&D leads who need clear reasoning in a rapidly changing field. GPCR innovation is accelerating. Those who learn now will shape the drugs others spend the next decade trying to understand. 40 years of expertise at your fingertips: Explore the full library ➤ Subscribe to the Kenakin Brief to stay in the know ➤

Developmental and homeostatic signaling transmitted by the G-protein coupled receptor FPR2. Progressive Technologies and Approaches Revealing Novel GPCR Biology and Drug Development Potential. FREE Symposium - IPI Surfacing (June 15, 2023) Training School on “Cell-based assays to study Adhesion I-GPCRNet (October 25 - 27, 2023) GPCR Jobs NEW Convergent Research - Senior Scientist, Cell-Based Assay Development NEW Post Doctoral Fellow NEW Research associate in protein production NEW Vice President

Recent studies have revealed that PGs play pivotal roles in embryo development, ciliogenesis, and organ During development, PGE2 signaling regulates embryogenesis, hepatocyte differentiation, hematopoiesis advances in understanding the functions and mechanisms of prostaglandin signaling in ciliogenesis, embryo development