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understanding why two drugs with similar affinity may behave completely differently , and how the secret lies Ligands don’t just “bind”—they change  the receptor. These sites don’t behave like traditional active sites. Ligands may take hours to equilibrate , even when they look potent on paper. What If the Same Site Behaves Differently Depending on the Ligand?

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These probes shift brightness and fluorescence lifetime as pH changes. Revvity commercial launch Building a Scalable Platform — Not a One-Off Assay The brilliance of pHSense lies “It’s like a funnel,” Trinquet explains. To hear the full story of how pHSense came to life—and why the GLP-1 data changed everything— 🎧 Listen GPCR X Revvity Collaboration ⸻ Want more like this? 👉 Join the Dr.

Liu S, Anderson PJ, Rajagopal S, Lefkowitz RJ, Rockman HA. Wodak SJ, Paci E, Dokholyan NV, Berezovsky IN, Horovitz A, Li J, et al. Motlagh HN, Wrabl JO, Li J, Hilser VJ. The ensemble nature of allostery. Shen S, Zhao C, Wu C, Sun S, Li Z, Yan W, et al. Truong ME, Bilekova S, Choksi SP, Li W, Bugaj LJ, Xu K, et al.

Can we leverage structural and computational insights not just to explain receptor–ligand interactions after the fact, but to forecast outcomes and design ligands with new properties? When existing compounds are exhausted, bespoke ligands are designed and synthesized in-house. Common questions in the group include: Can we forecast ligand efficacy or selectivity? But part of their rigor lies in restraint.

Receptors in Hepatic Stellate Cells and Approaches to Anti-Fibrotic Treatment of Non-Alcoholic Fatty Liver Disease The prevalence of non-alcoholic fatty liver disease (NAFLD) is globally increasing. Like many other organs, various GPCRs play a role in regulating liver function. It is predicted that more than 50 GPCRs are expressed in the liver. of the liver is very limited.

In particular, we focus on the application of on-cell NMR spectroscopy to characterize ligand interactions techniques allow for quantification of binding affinities, competitive binding assays, delineation of ligands involved in binding, ligand bound-state conformational determination, evaluation of receptor structuring and dynamics, and inference of distance constraints characteristic of the ligand-receptor bound state

Toll-like receptor 4 (TLR4) is one such non-GPCR receptor, which involves MyD88-dependent and TRIF-dependent

thoroughly investigated the role of single amino acid changes to clarify the molecular mechanisms governing ligand Rational Drug Design One immediate application of this research lies in rational drug design . Alternatively, allosteric modulators , which bind to sites outside the traditional ligand-binding pocket Interestingly, only 10 out of 82 important residues are within the ligand-binding pocket, resulting in Molecular determinants of ligand efficacy and potency in GPCR signaling.

Its strength lies not in complexity, but in the rigor of its simplicity. In the full lecture, Dr. Deviations—like reduced maximal responses or non-linear regressions—signal confounding kinetics, receptor Incomplete equilibration , where kinetics distort linearity. Each non-linearity is a coded message about the true mechanism. Explore the full library ➤

. 👉 Most founders don’t even realize they’re still running their company like an academic research group   ✅  This post explores how scientific thinking can become a leadership liability and what mindset But in the startup environment, these instincts can quickly become liabilities. Founders who keep operating like researchers often create internal confusion. It’s about realizing that your value now lies in decisions, not just in depth.    

Drug pipelines live and die by your ability to make fast, accurate calls. One wrong assumption about how your molecule behaves in a living system can sink months of work and millions In this session, you’ll gain: ✅ A mental model you can trust  for predicting how GPCR ligands behave Every ligand you design enters a system that is already balancing opposing forces—vasoconstriction vs When In Vitro Lies: The Patient vs.

GPCR-BSD: a database of binding sites of human G-protein coupled receptors under diverse states Fan Liu , Han Zhou , Xiaonong Li , Liangliang Zhou , Chungong Yu , Haicang Zhang , Dongbo Bu 🤩 Seriously, why GPCR Events to keep you informed and engaged GPCR Jobs connecting candidates with positions Direct line This strategic decision to limit free content is essential as we need to increase revenue to support

That gap leaves clinicians, first responders, and families without a reliable lifesaving tool in mixed With fentanyl, the danger lies in apneas —complete pauses in breathing. Naloxone’s Limits in the Age of Xylazine For decades, naloxone has been the trusted antidote for opioid First responders describe revivals that don’t feel like revivals, as if the body is still trapped in In other words, this is GPCR science with immediate, life-or-death consequences.

For receptor assays and the biological interpretation of ligands, he relies on a network of collaborators The power of this design lies not in its independence but in its interdependence . predictions, especially when burned in the past by models that promised too much and delivered too little His group is trained to explain exactly what a model can predict and where its limits are. 🎧 Listen to the full episode on the Dr.

structural analysis of these complexes revealed two important aspects: the specific residues involved in ligand between the receptor-Gs and receptor-Gi complexes, suggesting that the selectivity of the G-protein lies Likewise, in this work the authors identify for the first time the specific amino acids that modulate subfamilies of class A GPCRs and potential therapeutic targets that are activated by the same endogenous ligand Check the original article at this link https://pubmed.ncbi.nlm.nih.gov/35714614/ *Above information

Breakthroughs this week: FFA4 receptor signaling controls lipolysis at lipid droplets; novel atypical GPCR-arrestin complexes; Lilly's oral GLP-1, orforglipron, delivers weight loss of up to an average Career opportunities:  A curated list of new positions, including a Research Associate, a Senior Research If you’re not there, you’re missing out on the next wave of allosteric modulators, biased ligands, and This event is a critical opportunity to stay informed, but the real advantage lies in applying these

GPCR dimers in drug discovery referring to important conformational changes, allosteric properties, ligand Interestingly, the amplitude of the conformational changes due to ligand binding is limited at these Li, et al 2012; B. Bai, et al. 2014; B. Ji, et al. 2020; L. Wan, 2020). Various studies reported that the biased properties of ligands and receptors are a consequence of GPCR Junke Liu et al. recently provided key insights into GPCR oligomerization and biased signalling, using

At a molecular level, different ligands bind to the same receptor and vice-versa (Marcuzzi et al. 2018 Drug discovery is shifting towards the development of biased ligands, which promote the engagement of and signaling patterns, by modulating ligand binding, as well as G-protein coupling or interaction with , unlike most of the class A GPCRs ligands that are small molecules or short peptides. Overall, the future potential lies in using different therapeutic modalities to modulate the stromal

Structurally they characterize by a long extracellular region of adhesion-like domains which modulate structures provided the basis for the mechanism of self-activation of aGPCRs supporting the encrypted ligand possible to know that ADGRL3 can activate and form stable complexes with Gs, Gi, Gq, and G12, where like binding pocket and helps to stabilize the tethered ligand-receptor. Qian, Y., Ma, Z., Liu, C., Li, X., Zhu, X., Wang, N., Xu, Z., Xia, R., Liang, J., Duan, Y., Yin, H.,

N-terminal PTMs on chemokine receptors The interaction of chemokine receptors with their cognate chemokine ligands This PTM has been shown to be heterogeneous [Li X et al. 2018; Scurci I et al. 2021) and to improve the From the five GalNAc-Ts, GalNAc-T1 was shown to be the most likely candidate for directly glycosylating pairs and potentially cell line and tissue tested. In addition, tyrosine sulfation is heterogenous between cell lines or even on the same cell (Scurci I

solid preclinical package, promising safety data, and a consistent in vivo proof-of-concept, it feels like Founders who prepare to present  often miss the deeper expectation: the FDA is not just listening, it What the FDA Is Actually Optimizing For 👉 Biotech teams often treat the FDA like an evaluator. In reality, the FDA acts more like a systems-level risk assessor . indication selection to study design, should be filtered through the question: “What would this look like

. 👉 Opening with mechanisms forces the listener to do all the work. . ✅ Start with relevance, not results. 2️⃣ Using buzzwords instead of clarity Words like “platform”, Your listener doesn’t want to be impressed. If your listener doesn’t know what to do next or who should be involved, the conversation stalls. ✅ A Make it easy for the listener to understand what sets your approach apart from existing solutions or

PAMs permit enhancement without replicating the liabilities of orthosteric agonists. Endogenous ligands remain part of the signaling equation, preserving physiological patterning. Efficacy is not a molecule-only attribute—it's a joint property of ligand and system. High-coupled systems inflate apparent efficacy; low-coupled systems expose its limits. Dr. One carries broad off-target risk; the other behaves more like a high-affinity ligand with slow dissociation

GPCR signaling wasn’t linear. It wasn’t clean. shaped his partnership with JB, the chemist who would eventually help his lab visualize receptors in living They think in functional groups, fluorophores, linkers, and binding pockets. Instead of forcing antibodies to do what they weren’t built for, JB’s group engineered fluorescent ligands The signaling didn’t line up. The knockout behaved differently than expected.

. 👉 We’re talking about the type of quiet misalignment that appears to be progress but feels like confusion You assume your cofounder sees the same finish line you do. When these lines blur, so do accountability and execution. 3️⃣ The third and hardest shift is restoring Realignment as a Growth Lever, Not Just a Fix 👉 Most founders treat alignment like a hygiene issue. But because it ensures everyone is solving the same problem. ✅ If your biotech startup feels like it’

 to remotely control GPCR signaling with light. This was the moment when photopharmacology felt like the future. The literature was buzzing. Live-tissue dynamics become guesswork. This accidental tool changed that. And importantly, they liked working together. Scientific progress is rarely linear. But depth compounds.

Meanwhile, researchers in the building across the way turned off the lights at 6 PM.  vs. cell lines. They start with people you actually like working with . GPCR–islet signaling links extended beyond classical ligand models.Collaboration and long-term persistence Should patients stay on incretin therapies for life?

David Hodson walks through how his team uses fluorescence tools and chemically engineered ligands to Fluorescent ligand engineering clarifies receptor behavior that cell lines can’t reveal. Who should listen Researchers navigating complex datasets, balancing innovation with assay rigor, or Listen to the episode ➤ Quick Links Assess GPCR Biased Signaling of Agonist How GPCR Collaboration Built With live GPCR University courses returning next year and platform capabilities expanding, Premium pricing

Most labs operated like small, competing startups. That gave them capabilities others couldn’t match — from receptor biosensor platforms to live-cell imaging Weekly seminars were mandatory but lightweight, designed to connect  rather than perform. It’s a competitive advantage. 🎧 Listen to the full episode:   Leadership, Luck, and GPCR Signaling 🔓