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depression, schizophrenia and Parkinson’s disease. [1,2] Several dopamine ligands have been approved as drugs Therefore, both assays can be used for fundamental D3 receptor-ligand binding studies as well as for drug methods can increase the quality and quantity of both fundamental receptor research and high-throughput drug Current Drug Treatments Targeting Dopamine D3 Receptor.

However, in drug discovery projects, perfection can’t be attained soon enough. A project to develop a perfect drug, or a drug that is as safe and effective as possible, may never begin If only Voltaire were here today to see how drug discovery is being accelerated by new technologies. Several new technologies that are being used to accelerate drug discovery are highlighted in this article receptors (GPCRs) to enable the discovery of agonistic biologics; and automated instrumentation that

Historically, drug discovery efforts targeting GPCRs focused on G-protein-dependent signaling pathways discovery. discovery (Eishingdrelo & Kongsamut, 2013). Minireview: targeting GPCR activated ERK pathways for drug discovery. Biased receptor signaling in drug discovery. Pharmacological Reviews, 71(2), 267-315.

Hello Dr.GPCR readers! This is Lucía from the Celtarys Research chemistry team.  For our very first post in this ecosystem, we wanted to highlight a huge part of our work at Celtarys Research: conjugation strategies. You can check what we do here on our website!   Conjugation strategies for small molecules are very versatile! In this case, we would like to focus on the synthesis of fluorescent probes. Traditionally, the most reliable and commonly used method is the amide coupling  using acid and amine .[ 1 ] This method has several advantages: it is usually very robust, good yields, reagents are found in most chem labs (like HATU, HoBT, EDCI etc.). Still, there are some downsides, such as the byproduct obtained by the O-acylisourea rearranging intramolecularly into the N-acylurea.[ 2]     NHS ester amide coupling  is the most suited for bioconjugation with proteins, DNA, etc, thanks to its reaction with the free amino groups present in these biomolecules. NHS esters are not very stable even in aqueous environment but they only need a slightly basic medium for the reaction to work, so they have to be used quickly and stored correctly. Not only do they work in aqueous medium, but also in aprotic solvents like DMF, where you will need to add a base such as TEA. [ 3]     Maleimide  conjugation with thiols  present Cys residues. This conjugation is very useful for tagging biomolecules and can also be used to develop fluorescent probes with small molecules. Its biggest advantage is the presence of Cys residues in proteins, although sometimes S-S bridge reduction is needed, and how quickly the reaction takes place. The biggest detractor? It’s reversible under non-reducing conditions. [ 4]     Other strategies include click chemistry,  more specifically, the CuAAC (Cu(I)- catalyzed azide-alkyne 1,3-dipolar cycloaddition), which is a very robust conjugation strategy to obtain linkers with a rigid moiety (the triazol). But it also presents some issues, such as synthesizing the as the presence of the copper catalyst, which has to be removed completely, otherwise it can quelate biomolecules or induce cell toxicity. [ 5]     At Celtarys’ we have our conjugation strategy - our own proprietary technology- which bypasses some of the issues seen before. There’s no need for any catalysts; all reagents will be incorporated in the structure of the final compound. The reaction is convergent, efficient and robust. Thanks to the unique linker structure we obtain, which can be divided into three differentiated parts, we can modify the rigidity of the linker as well as the physicochemical properties of the whole probe. This property comes from the wide chemical space this reaction can access – we can substitute one reagent and make an unprecedented combination, also using commercially available precursor, which improves the performance of the probes.  It also poses some disadvantages – just like acid-amine amide coupling, some byproducts are obtained during the synthesis. However, these are usually easily removable. Besides, it’s an eco-friendlier method, which always helps future-proof our probes!  References   (1) Brown, D. G.; Boström, J. Analysis of Past and Present Synthetic Methodologies on Medicinal Chemistry: Where Have All the New Reactions Gone?: Miniperspective. J. Med. Chem.   2016 , 59  (10), 4443–4458. https://doi.org/10.1021/acs.jmedchem.5b01409 .   (2) Sam, S.; Touahir, L.; Salvador Andresa, J.; Allongue, P.; Chazalviel, J.-N.; Gouget-Laemmel, A. C.; Henry De Villeneuve, C.; Moraillon, A.; Ozanam, F.; Gabouze, N.; Djebbar, S. Semiquantitative Study of the EDC/NHS Activation of Acid Terminal Groups at Modified Porous Silicon Surfaces. Langmuir   2010 , 26  (2), 809–814. https://doi.org/10.1021/la902220a .   (3) Fan, J.; Toth, I.; Stephenson, R. J. Chapter Three - Bioconjugated Materials in the Development of Subunit Vaccines. In Comprehensive Analytical Chemistry ; Verma, S. K., Das, A. K., Eds.; Elsevier, 2023; Vol. 103, pp 59–103. https://doi.org/10.1016/bs.coac.2023.02.005 .   (4) Fontaine, S. D.; Reid, R.; Robinson, L.; Ashley, G. W.; Santi, D. V. Long-Term Stabilization of Maleimide–Thiol Conjugates. Bioconjugate Chem.   2015 , 26  (1), 145–152. https://doi.org/10.1021/bc5005262 .   (5) Meldal, M.; Tornøe, C. W. Cu-Catalyzed Azide−Alkyne Cycloaddition. Chem. Rev.   2008 , 108  (8), 2952–3015. https://doi.org/10.1021/cr0783479 .

High-throughput approaches used in drug discovery create large datasets regarding ligand synthesis and Artificial intelligence in GPCR drug discovery The use of AI in GPCR drug discovery has increased over AI is providing a dramatic acceleration of the drug discovery process at multiple stages: 1. Instead, it complements and assists researchers in the GPCR drug discovery process. discovery.

GPCRs continue to be regarded as one of the most tractable classes of drug targets and are targeted by 30%–40% of current drugs (Hauser et al., 2017), with annual sales of GPCR-targeting drugs in 2018 accounting Despite this high number of GPCR targeted drugs, only a small portion (∼110) of the human GPCRome (consisting of approximately 850 GPCRs) has been successfully drugged, and obtaining highly potent and selective

The goal is to accelerate receptor-targeted discovery. Explore the partnership Multiplexing GPCR Discovery - Sakmar Lab’s Toolkit Goes Public The latest podcast

GPCR News delivers a toolkit of practical innovations—from drug design strategies that anticipate physiological Breakthroughs this week: Lilly to build $5B manufacturing facility in Virginia; Novo Nordisk flags drug Terry's Corner – Designing Drugs That Anticipate Physiological Pushback Most GPCR programs don’t fail GPCR , our mission is simple but urgent: Accelerate GPCR biology and drug discovery by connecting scientists GPCR scientists, translational pharmacologists, biotech discovery teams, and decision-makers who need

. _________________ Keyword Cloud: GPCR research community , chronic pain , GPCR drug discovery , GPCR

rise in biotech in recent years as researchers have discovered the vast potential for GPCR-targeting drugs struck a research agreement to discover new GPCR targets that’ll fuel the development of potential drug of the strategic collaboration weren’t released, but Sosei Heptares’ past two team-ups in GPCR-based drug discovery have clocked in at $1 billion—with Genentech—and, just last November, $2.6 billion in a partnership

Studying cancer-related proteins (BCL2 family), he combined NMR and molecular docking to explore drug From Empty Lab to GPCR Discovery Starting in an empty lab with just a shared desk, Alessandro and Antonella

Drugs that look great in vitro fall apart in humans.

receptors (GPCRs) play critical roles in human physiology and are one of the prime targets for marketed drugs While traditional drug discovery programs have focused on the development of ligands targeting the binding insights, together with the plethora of GPCR structures available today, will facilitate structure-based discovery current strategies for the identification of allosteric sites as well as ligand-based and structure-based drug discovery and design."

deep academic research, startup life, and the application of machine learning and pharmacology to GPCR drug discovery. discovery landscape. The company’s goal is to model receptor dynamics — including biased signaling — to predict drug behavior early career redirection to startup setbacks, each step has added new layers to his thinking about drug

Target-based screening is now a fundamental pillar of drug development, and GPCRs are key targets for This makes them very useful for GPCR drug discovery, since receptors are a lot bigger than their small Optimizing GPCR Drug Discovery with Fluorescence Polarization: Key Advantages and Future Perspectives Contact us  to drive further advancements in GPCR drug discovery!   Target-based drug discovery: Applications of fluorescence techniques in high throughput and fragment-based

assumptions to interpret allosteric binding data, you're likely missing critical insights—or mislabeling your drug Unlock “Allosteric Binding” Now Only in Terry’s Corner Why Terry’s Corner Drug discovery isn’t slowing built for scientists who want to move faster , think sharper , and make smarter decisions  in early discovery

Why Pipeline Efficiency Starts with Physiology Drug discovery doesn’t happen in a vacuum. Reflexes as Drug Design Partners Not all reflexes are enemies. Some can make a mediocre drug shine. This insight has huge implications for how you select and rank agonists in discovery campaigns. But drug discovery isn’t static — it’s a moving target. discovery experience If you’re serious about derisking your pipeline, this is where you sharpen the

Transmembrane domains of GPCR dimers – a novel hot spot for drug discovery G-protein-coupled receptors GPCR dimers are therefore emerging drug targets in different therapeutic areas including depression, In this study Xin Cai et al. highlight the importance of GPCR dimers in drug discovery referring to important What is the potential of targeting GPCR dimer interface in drug discovery? discovery targeting GPCR dimers.

Every September, Boston welcomes the global biotech and drug discovery community. discovery. discovery. Axxam Axxam is a leading provider of integrated discovery services, supporting the entire drug discovery discovery.

Welcome GPCR Fans,   In GPCR-targeted drug discovery, precision isn’t optional—it’s a requirement. Upcoming events : Lab-in-the-Loop AI-powered hit discovery (July 29); 5th Transatlantic GPCR Symposium At this international meeting, leaders shared next-gen strategies shaping modern drug discovery: Prof Scientists, drug discovery teams, and pharmacologists who need curated, career-relevant updates. Those acting on the right insights now will define the next wave of discovery.

help researchers move faster with custom fluorescent ligands, translational insight, and tool-enabled discovery

For discovery teams, this means a shorter exposure can yield longer efficacy windows—opening doors to Kenakin  will get released next month, featuring real questions from discovery scientists tackling enzyme Join Terry’s Corner and get: Frameworks proven in real discovery programs On-demand lessons  designed That’s why discovery teams turn to Terry’s Corner: to build strategies that anticipate these collisions Direct input  on future sessions—so topics match the hurdles your team faces in discovery and development

What emerged wasn’t just another pharmacology group — it became a collaborative engine for GPCR discovery Most GPCR discoveries aren’t blocked by science — they’re blocked by structures that make sharing hard And for those shaping the next generation of GPCR discovery — from AI integration to next-gen biosensors

Upcoming events:   Preview of Discovery on Target 2025 (Boston, Sept 24‑25), including GPCR‑Track breakout Snapshot of roles spanning PhD entry points to senior translational pharmacology—Protein Expression, Drug Discovery Scientist, and Staff Scientist in Molecular Pharmacology—curated with notes on fit, skill See the full guide and example ligands ➤ Discovery on Target 2025 Speaker Spotlight: Solubilization, GPCR scientists, translational pharmacologists, biotech discovery teams, and decision-makers who need

July 2022 "Orion Biotechnology and Peptilogics are pursuing AI-driven drug discovery to explore new functional

For metabolic GPCRs (like GLP-1 and GIP receptors): Drug efficacy depends on which cells express the :  Shared widely → now used globally to map GPCR activity in live systems The success wasn’t in the discovery Clarify brain vs. peripheral contributions to metabolic therapy Guide how next-generation incretin drugs

June 2022 "Ottawa, Canada, May 10, 2022 — Orion Biotechnology Canada Ltd, a drug discovery and development Oliver Hartley, Orion’s Vice-President Drug Discovery, will present Orion’s novel technology for targeting His presentations will describe Orion’s drug discovery platform, one of the fastest drug discovery solutions OB-004, demonstrating the ability of this powerful platform to rapidly identify best-in-class GPCR drug

predictions—a sentiment that highlights the skepticism that still exists around modeling in some corners of drug discovery.   As predictive modeling matures, its role will continue to expand, guiding ligand discovery, informing For early-career researchers, the takeaway is direct: GPCR drug discovery will increasingly depend on

Elevate Your GPCR Science with Essential Frameworks for Precision Drug Discovery: An Insight into Advanced Terry's Corner - Demystifying Antagonism: The Key to Precision Drug Discovery Understanding the nuances of competitive versus non-competitive antagonism is a cornerstone of effective drug discovery. , Not Breakdowns In the fast-paced world of GPCR drug discovery, the "go fast" mindset can often lead GPCR-Based Drug Discovery conference is where the future of GPCR therapies will be defined.

Watch Episode 175 If your model can’t predict the future of GPCR drug discovery, why build it at all? His lab sits at the crossroads of structure-based modeling, computational chemistry, and drug discovery Carlsson also runs a consulting arm  that advises drug discovery teams on GPCR modeling strategy. For drug discovery executives, the message is clear: predictive modeling can shorten timelines, reduce The next frontier in GPCR drug discovery isn’t more structures—it’s smarter models.