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G protein-coupled receptors (GPCRs) have been shown to play integral roles in Alzheimer's disease pathogenesis However, it is unclear how diverse GPCRs similarly affect Aβ and tau pathogenesis. GPCRs share a common mechanism of action via the β-arrestin scaffolding signaling complexes, which not only serve to desensitize GPCRs by internalization, but also mediate multiple downstream signaling events As signaling via the GPCRs, β2-adrenergic receptor (β2AR), and metabotropic glutamate receptor 2 (mGluR2

Chemokine receptors (CKRs) belong to a subfamily of G-protein-coupled receptors (GPCRs) and play a crucial helix (TM7) near ECL3, while the other links TM3 with ECL2, which is common to the broader class A GPCR Activation in Class A GPCRs Ligand binding in the orthosteric site leads to diverse activation mechanisms In addition, it has a glutamate residue at position 3.45, which is not found in human class A GPCRs, Check the original article at https://pubmed.ncbi.nlm.nih.gov/37212620/ #GPCR #DrGPCR #Ecosystem

ubiquitously expressed membrane proteins that associate with different G protein–coupled receptors (GPCRs ), including the parathyroid hormone 1 receptor (PTH1R), a class B GPCR and an important modulator of These data uncover a critical role of RAMPs in the activation and signaling of a GPCR that may provide a new venue for highly specific modulation of GPCR function and advanced drug design." Read more at the source #DrGPCR #GPCR #IndustryNews

"Fluorescently labeled ligands are versatile molecular tools to study G protein-coupled receptors (GPCRs targeting the intracellular allosteric binding site (IABS) of the CC chemokine receptor 2 (CCR2), a class A GPCR that has been pursued as a drug target in oncology and inflammation. reported intracellular CCR2 antagonists, several tetramethylrhodamine (TAMRA)-labeled CCR2 ligands were designed Read more at the source #DrGPCR #GPCR #IndustryNews

Therapeutics Announces the Formation of a Scientific Advisory Board comprising international leaders in GPCRs pharmacology, immunology, drug discovery and development for auto-immune diseases" Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 "G protein-coupled receptors (GPCRs) are signaling hubs in cell membranes that regulate a wide range of physiological processes and are popular drug targets. Serotonin1A receptors are important members of the GPCR family and are implicated in neuropsychiatric To explore the role of cholesterol in lateral dynamics of GPCRs, we utilized single particle tracking Read more at the source #DrGPCR #GPCR #IndustryNews

Three G-protein coupled receptors (GPCRs) for galanin have been discovered, which is the focus of efforts To understand the basis of the ligand preferences of the receptors and to assist structure-based drug design, we used cryo-electron microscopy (cryo-EM) to solve the molecular structure of GALR2 bound to Read more at the source #DrGPCR #GPCR #IndustryNews

underlying non-alcoholic fatty liver disease (NAFLD) have yet to be fully delineated and only a single drug Signaling 7 (RGS7) in hyperlipidemia-dependent hepatic dysfunction. " Read more at the source #DrGPCR #GPCR

selectivity/biased signaling has led to the discovery of biased compounds as both research tools and novel drugs A major pan-receptor focus has been to identify GPCR-selective ligands that have bias in G protein-dependent Read more at the source #DrGPCR #GPCR #IndustryNews

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 .

In this review, we focus on recent advances in G-protein-coupled receptor (GPCR) targets. receptor-4 (MC4R), adhesion, lysophosphatidic acid (LPA) and smoothened (Smo) receptors to initiate new drug-screening

introduced Basecamp Bio, a wholly owned subsidiary dedicated to fueling ShouTi’s pipeline and pursuing drug Read more at the source #DrGPCR #GPCR #IndustryNews

Why Asking Better Questions in Science Improves the Work Itself For JB, questions fuel the way he designs In his collaboration with David Hodson, every major leap—from early ligand design to GPCR visualization Throughout his own journey—from organic chemistry to chemical biology to GPCR imaging—every pivotal step  🎧 Listen to the full episode https://www.ecosystem.drgpcr.com/dr-gpcr-podcast/chemical-probes-for-gpcr-imaging-and-internalization

Pathways "Adhesion G protein-coupled receptor A1 (ADGRA1) belongs to the G protein-coupled receptor (GPCR pathways in amygdalae of male mice, implicating a potential, therapeutic application in novel anti-anxiety drug Read more at the source #DrGPCR #GPCR #IndustryNews

Combination index was analyzed for the combination of fentanyl and chemotherapeutic drugs. Read more at the source #DrGPCR #GPCR #IndustryNews

neurotransmitters in the normal neural and the GBM microenvironments, and discuss potential targeted drugs Read more at the source #DrGPCR #GPCR #IndustryNews

systems pharmacology (QSP) modeling is an emerging mechanistic computational approach that couples drug It has begun to play important roles in drug development for complex diseases such as cancer, including Read more at the source #DrGPCR #GPCR #IndustryNews

These can be used either as stand-alone therapeutics or to improve the safety profile of opioid drugs electrophysiological recordings to evaluate the effects of YM-254890 on the excitability of dorsal root ganglion (DRG Read more at the source #DrGPCR #GPCR #IndustryNews

demonstrate that the chemoreceptor genes, srg-36 and srg-37, which encode G protein-coupled receptors (GPCRs Here, we show that SRG-36 and SRG-37 act as upstream GPCRs that activate EGL-30. SRG-36 and SRG-37 are GPCRs for the dauer-inducing ascaroside, ascr#5. Thus, ascaroside signaling promotes axon regeneration by activating the GPCR-Gqα pathway.

Food and Drug Administration (FDA) approval of TAVNEOS in October 2021. Read more at the source #DrGPCR #GPCR #IndustryNews

ADXN, Nasdaq: ADXN), a clinical-stage pharmaceutical company pioneering allosteric modulation-based drug media at 16:00 CET (15:00 GMT / 10:00 EST / 07:00 PST) the same day. " Read more at the source #DrGPCR #GPCR

cancer therapies focuses on processes such as angiogenesis, cell signaling, stemness, metastasis, and drug Moreover, the use of propranolol in combination therapies with other drugs has shown synergistic antitumor Read more at the source #DrGPCR #GPCR #IndustryNews

allosteric binding site (IABS) has recently been identified at several G protein-coupled receptors (GPCRs To chemically induce CCR9 degradation, we then developed the first PROTAC targeting the IABS of GPCRs our CCR9-PROTAC is able to reduce CCR9 levels, thereby offering an unprecedented approach to modulate GPCR

in TMC Score of 3.2 Units in Valbenazine-Treated Patients- Company Plans to Submit Supplemental New Drug Food and Drug Administration in 2022 SAN DIEGO, Dec. 7, 2021 /PRNewswire/ -- Neurocrine Biosciences ( " Read more at the source #DrGPCR #GPCR #IndustryNews

under methylphenidate treatment but responded positively to 3 mg per day of the atypical neuroleptic drug Read more at the source #DrGPCR #GPCR #IndustryNews

Food and Drug Administration (FDA) that the study may proceed. Read more at the source #DrGPCR #GPCR #IndustryNews

SIX and Nasdaq: ADXN), a clinical-stage pharmaceutical company pioneering allosteric modulation-based drug developing novel oral gamma-aminobutyric acid subtype B (GABAB) positive allosteric modulator (PAM) drug compounds for Charcot-Marie-Tooth type 1A neuropathy (CMT1A) and pain. " Read more at the source #DrGPCR #GPCR

role, she will focus on the application of artificial intelligence (AI), machine learning, and the design of protein structures in the discovery and development of novel drug candidates. Read more at the source #DrGPCR #GPCR #IndustryNews

therapeutic targets in Uterine Corpus Endometrial cancer "Adhesion G protein-coupled receptors (adhesion GPCRs ), as a member of the G protein-coupled receptors (GPCRs) superfamily, have gradually entered the field The structure, function, and involvement of adhesion GPCRs in cancer development have been discussed alsooneofthemostcommonfemalereproductivesystemtumors, but there are few pieces of research related to adhesion GPCRs Read more at the source #DrGPCR #GPCR #IndustryNews

signaling is transduced by a multikinase-dependent switch controlling the apico-basal distribution of the GPCR smoothened "The oncogenic G-protein-coupled receptor (GPCR) Smoothened (SMO) is a key transducer of of HH to the apico-basal distribution of SMO and provide a novel mechanism for the regulation of a GPCR Read more at the source #DrGPCR #GPCR #IndustryNews