The critical player is Apurinic/Apyrimidinic Endodeoxyribonuclease 2 (APEX2). enzyme that catalyzes the oxidation of specific substrates in the presence of hydrogen peroxide (H 2 O 2 ). When AUR is oxidized by APEX2 in the presence of H 2 O 2 , it produces a fluorescent product that can For further details, refer to the full article: DOI: 10.1038/s41589-024-01705-2

September 2022 "Serotonin receptor 5-HT2A and tropomyosin receptor kinase B (TrkB) strongly contribute

introducing the concept of 'unproductive coupling'[1] and a fascinating phenomenon known as GPCR priming [2] coupling efficiency of cognate G proteins to GPCRs, thereby amplifying canonical downstream signalling [2] Gq was not important for the increased β2AR-Gs-mediated cAMP levels in response to isoproterenol. [2] Proc Natl Acad Sci U S A, 2020. 117(35): p. 21723-21730. 2.      ., Purinergic Receptor Transactivation by the β(2)-Adrenergic Receptor Increases Intracellular Ca(2+)

receptors on B cells and intracellular β2-ADR downstream molecules (G protein-coupled receptor kinase 2 (GRK-2), β-Arrestin 2, p38 MAPK, extracellular signal-regulated kinase 1/2 (ERK1/2) and cAMP response Moreover, we observed a profound downregulation of GRK-2 shortly after induction of arthritis and an increase in β-Arrestin 2 only at late stage of arthritis. cells with the β-ADR agonist terbutaline increased pp38 MAPK independent of the timepoint, while pERK1/2

We synthesized and characterized a novel A2AAR antagonist, 2 (LJ-4517), with Ki = 18.3 nM. X-ray crystallographic structures of 2 in complex with two thermostabilized A2AAR constructs were solved at 2.05 and 2.80 Å resolutions. In contrast to A2AAR agonists, which simultaneously interact with both Ser2777.42 and His2787.43, 2 only The n-hexynyl group of 2 extends into an A2AAR exosite.

October 2022 "CXCR1 and CXCR2 chemokine receptors, mainly activated by interleukin 8 (IL-8 or CXCL8), Much focus is currently being directed towards CXCR1/2 inhibitors, as these receptors primarily induce CXCR1/2 inhibitors show beneficial effects in various animal models of CVD. Based on these encouraging results, testing CXCR1/2 inhibitors in clinical trials could be of a great

August 2022 "CXCR1 and CXCR2 chemokine receptors, mainly activated by interleukin 8 (IL-8 or CXCL8), Much focus is currently being directed towards CXCR1/2 inhibitors, as these receptors primarily induce CXCR1/2 inhibitors show beneficial effects in various animal models of CVD. Based on these encouraging results, testing CXCR1/2 inhibitors in clinical trials could be of a great

Pharmacological Reviews, 71(2), 267-315. Lu, N., & Malemud, C. J. (2019). Biology of the Cell, 93(1‐2), 71-79. Wei, H., Ahn, S., Shenoy, S. K., Karnik, S. J. (2003). Independent β-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2.

October 2022 Use of CRISPR/Cas9-edited HEK293 cells reveals that both conventional and novel protein In this study, we generated and characterized human embryonic kidney 293A (HEK293A) cell lines devoid Additionally, using the Gαq/11 inhibitor YM-254890, GPCR kinase 2 and 3 (GRK2 and GRK3) KO cells, and a receptor containing a mutated putative adaptor protein complex 2 (AP-2) interaction motif, we demonstrate and AP-2 (29%), but not GRK3.

is more associated with the analgesic effect, while the side effects are orchestrated via β-arrestin 2. However, opioids that prevent recruiting β-arrestin 2 do not address the problem since ligands that only minimally recruit β-arrestin 2 to MORs may also cause opioid side effects2. that endogenously expresses MOR and was modified through CRISPR/Cas9 to knock out β-arrestin 1 and 2 PMID: 8390660; PMCID: PMC46725. https://pubmed.ncbi.nlm.nih.gov/35435616/ 2.

September 2022 GPCR/endocytosis/ERK signaling/S2R is involved in the regulation of the internalization G protein-coupled receptors (GPCR), endocytosis pathways, extracellular signal-regulated kinases 1/2 (ERK1/2) signaling, p38 signaling, mitochondrial respiration and Na+/K+-ATPase activity on the uptake We performed a siRNA knockdown (KD) to assess the effect of Sigma-2 receptor (S2R) /Transmembrane Protein The inhibitors of GPCR, ERK1/2, phagocytosis, and clathrin-mediated endocytosis (CME) as well as siRNA

Key GPCRs Driving Gastrointestinal and Immune Disorders Inversago Pharma Doses First Patient in Phase 2 Sosei Heptares' Partner Pfizer Progresses its Oral GLP-1 Receptor Agonist PF-07081532 into Phase 2 Clinical Trials for Treating Type 2 Diabetes and Obesity Special report 2022: Meet 20 women blazing trails in GPCR Events, Meetings, and Webinars 2nd GPCR-Targeted Drug Discovery Summit | February 21-23, Boston. June 11-16, 2023. 19th World Congress of Basic & Clinical Pharmacology 2023. July 2 - 7.

August 2022 "Emerging evidence suggests that G protein-coupled receptor (GPCR) kinases (GRKs) are associated Significantly, we show that GRKs generate distinct phosphorylation barcodes in intracellular loop 2 ( terminus of APH1A, which differentially regulate recruitment of the scaffolding protein β-arrestin 2

of the alpha subunit contributing to the termination of the G protein-mediated signaling cascades[1, 2] protein-binding domain, the DEP (Dishevelled, Egl-10 and Pleckstrin domain) domain, and the GoLoco motif[2, structural motifs have been shown to alter the specificity and potency of the RGS-GPCR interaction[2] Cell, 1997. 89(2): p. 251-61. https://pubmed.ncbi.nlm.nih.gov/9108480/ 2. Genomics, 2021. 113(4): p. 2134-2144. https://pubmed.ncbi.nlm.nih.gov/33845140/

explain the discovery of a novel inverse agonist at the cannabinoid receptor 2. G. (2017). M. (2024). Flipping the GPCR switch: Structure-based development of selective cannabinoid receptor 2 inverse agonists Extracellular loop 2 of the adenosine A1 receptor has a key role in orthosteric ligand affinity and agonist

October 2022 "Pepducins are small-lipidated peptides designed from the intracellular loops of G protein-coupled Over the past 2 decades, pepducins have progressed initially from pharmacologic tools used to manipulate site-independent manner to compounds with therapeutic potential that have even been used safely in phase 1 and 2

October 2022 Successful prednisolone or calcimimetic treatment of acquired hypocalciuric hypercalcemia (pertussis toxin-sensitive G proteins, whose βγ subunits activate multiple signals, including ERK1/2) We here describe 3 patients with symptomatic AHH who shared characteristics with the 2 cases we previously

October 2022 "Systolic heart failure (HF) is a chronic clinical syndrome characterized by the reduction as they pertain to modulation of cardiac function in the context of chronic HF, by focusing on the 2 and a half that highlight the emerging roles of the GPCR-kinases and the β-arrestins in the adrenals, 2

We investigated the feasibility of this lipophilic entry route for 2-iodomelatonin, a nonselective agonist dissociation rate from the MT2 receptor, applying enhanced sampling simulations and free-energy calculations. 2- unbinding it frequently assumes an open conformation in the MT1 but not in the MT2 receptor, favoring 2-

phosphorylation have been pivotal in deciphering GPCR activity, particularly in drug discovery endeavors [2] Annu Rev Biochem, 1987. 56: p. 615-49. 2.      Nat Methods, 2005. 2(3): p. 177-84. 7.      J Biol Chem, 2018. 293(19): p. 7466-7473. 8.      J Biol Chem, 2007. 282(14): p. 10576-84. 13.   

September 2022 Opposite Effects of Src Family Kinases on YAP and ERK Activation in Pancreatic Cancer siRNA)-mediated knockdown of YES1 and transfection of epitogue-tagged YAP mutants in PANC-1 and MiaPaCa-2 potently and synergistically inhibited colony formation by PDAC cells and suppessed the growth of MiaPaCa-2

Several molecules from the SNARE complex, including vesicle-associated membrane protein 2 (VAMP2), regulate In addition, VAMP2 can interact with other GPCRs, such as the beta-2 adrenergic receptor and the mu-opioid www.ecosystem.drgpcr.com/structural-and-molecular-insights-into-gpcr-function/vesicle-associated-membrane-protein-2- Puthenveedu. 2021. Ma. 2008.

demonstrated for receptors such as the parathyroid hormone receptor (PTHR) and the vasopressin receptor 2 Drug discovery today, 24(11), 2192–2201. https://doi.org/10.1016/j.drudis.2019.09.003 Ferrandon, S., Independent beta-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2. Nature communications, 8(1), 443. https://doi.org/10.1038/s41467-017-00357-2 Jong, Y.

Some neuronal GPCRs (such as GTR-1, DCAR-1, DOP-2, NPR-8, NPR-12, NPR-9, and DAF-37) functioned upstream of GOA-1, some neuronal GPCRs (such as DCAR-1, DOP-2, NPR-9, NPR-8, and DAF-37) functioned upstream of GSA-1, and some neuronal GPCRs (such as DOP-2, NPR-8, DAF-37, and DCAR-1) functioned upstream of GPA

October 2022 "Melanocortin 3 receptor (MC3R) is a G-protein coupled receptor (GPCR) that is defined importance of the MC3R regulations in three main concepts: 1) its impact on weight and appetite control, 2)

August 2022 Structure Therapeutics Extends Financing, Advances Diabetes and Obesity Clinical Program and Changes Name from ShouTi " San Francisco and Shanghai – August 1, 2022 – Structure Therapeutics million financing round, extending its $100 million Series B financing, which was announced in October 2021 Therapeutics has completed dosing in a single ascending dose (SAD) Phase 1 study of its lead type 2

August 2022 GRK2 selectively attenuates the neutrophil NADPH-oxidase response triggered by β-arrestin The medium chain fatty acid receptor GPR84 as well as formyl peptide receptor 2 (FPR2), receptors expressed

January 2022 Inversago Pharma Completes Phase 1 Clinical Trial on First-in-Class, Peripheral CB1 Blocker and Provides Strategy Update "Company has completed the Phase 1 Clinical Trial for its INV-202 molecule Encouraging Phase 1 results and supportive preclinical package assist in the launch of Phase 2 clinical blockade company, announced today the successful completion of the Phase 1 Clinical Trial for its INV-202 the trial warrant further investigation, and the Company will actively pursue the advancement of INV-202