PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 32234810-0 2020 A New Paroxetine-Based GRK2 Inhibitor Reduces Internalization of the mu-Opioid Receptor. Paroxetine 6-16 G protein-coupled receptor kinase 2 Homo sapiens 23-27 33568523-0 2021 Paroxetine-mediated GRK2 inhibition is a disease-modifying treatment for osteoarthritis. Paroxetine 0-10 G protein-coupled receptor kinase 2 Homo sapiens 20-24 33158816-6 2021 Pharmacological inhibition of GRK2 by the clinically approved antidepressant, serotonin reuptake inhibitor paroxetine (PX), recapitulated the effects of GRK2-silencing with dose- and time-dependent IGF-1R downregulation without associated beta-arr-BS. Paroxetine 107-117 G protein-coupled receptor kinase 2 Homo sapiens 30-34 33158816-6 2021 Pharmacological inhibition of GRK2 by the clinically approved antidepressant, serotonin reuptake inhibitor paroxetine (PX), recapitulated the effects of GRK2-silencing with dose- and time-dependent IGF-1R downregulation without associated beta-arr-BS. Paroxetine 107-117 G protein-coupled receptor kinase 2 Homo sapiens 153-157 33158816-6 2021 Pharmacological inhibition of GRK2 by the clinically approved antidepressant, serotonin reuptake inhibitor paroxetine (PX), recapitulated the effects of GRK2-silencing with dose- and time-dependent IGF-1R downregulation without associated beta-arr-BS. Paroxetine 119-121 G protein-coupled receptor kinase 2 Homo sapiens 30-34 33158816-6 2021 Pharmacological inhibition of GRK2 by the clinically approved antidepressant, serotonin reuptake inhibitor paroxetine (PX), recapitulated the effects of GRK2-silencing with dose- and time-dependent IGF-1R downregulation without associated beta-arr-BS. Paroxetine 119-121 G protein-coupled receptor kinase 2 Homo sapiens 153-157 33372534-0 2021 Paroxetine Attenuates Cardiac Hypertrophy Via Blocking GRK2 and ADRB1 Interaction in Hypertension. Paroxetine 0-10 G protein-coupled receptor kinase 2 Homo sapiens 55-59 33372534-5 2021 Meanwhile, we discovered a selective serotonin reuptake inhibitor paroxetine specifically blockades GRK2 and ADRB1 interaction. Paroxetine 66-76 G protein-coupled receptor kinase 2 Homo sapiens 100-104 33372534-11 2021 Conclusions Paroxetine promotes ADRB1 sensitivity and attenuates cardiac hypertrophy partially via blocking GRK2-mediated ADRB1 activation and internalization in the context of hypertension. Paroxetine 12-22 G protein-coupled receptor kinase 2 Homo sapiens 108-112 31506468-0 2019 Computational study of paroxetine-like inhibitors reveals new molecular insight to inhibit GRK2 with selectivity over ROCK1. Paroxetine 23-33 G protein-coupled receptor kinase 2 Homo sapiens 91-95 31506468-5 2019 We have performed molecular docking, three dimensional quantitative structure activity relationship (3D-QSAR), molecular dynamics (MD) simulation, and free energy calculations techniques on a series of 53 paroxetine-like compounds to understand the structural properties desirable for enhancing the inhibitory activity for GRK2 with selectivity over ROCK1. Paroxetine 205-215 G protein-coupled receptor kinase 2 Homo sapiens 323-327 30366961-9 2018 The ability of bisindolylmaleimide I and paroxetine to block some of these actions suggested the activation of protein kinase C was associated mainly with the action of PMA, whereas G protein-coupled receptor kinase (GRK) 2 (GRK2) was involved in the action of the three agents. Paroxetine 41-51 G protein-coupled receptor kinase 2 Homo sapiens 182-223 29980659-6 2018 Preincubation with the GRK2 inhibitor paroxetine almost completely prevented desensitization of UTP- and attenuated desensitization of AngII-stimulated arterial contractions. Paroxetine 38-48 G protein-coupled receptor kinase 2 Homo sapiens 23-27 30018141-5 2018 Interestingly, siRNA-mediated depletion of G protein-coupled receptor kinase-2 (GRK2) or inhibition by the GRK2-specific inhibitor, paroxetine, inhibited TCR-induced phosphorylation of CXCR4-Ser-339 and TCR-CXCR4 complex formation. Paroxetine 132-142 G protein-coupled receptor kinase 2 Homo sapiens 107-111 29980659-10 2018 In human uterine smooth muscle cells, paroxetine reversed GRK2-mediated histamine H1 receptor desensitization, but not GRK6-mediated oxytocin receptor desensitization. Paroxetine 38-48 G protein-coupled receptor kinase 2 Homo sapiens 58-62 29070696-3 2017 Previously, we discovered two classes of GRK2-selective inhibitors, one stemming from GSK180736A, a Rho-associated coiled-coil containing kinase 1 (ROCK1) inhibitor, the other from paroxetine, a selective serotonin-reuptake inhibitor. Paroxetine 181-191 G protein-coupled receptor kinase 2 Homo sapiens 41-45 30463058-3 2018 Small molecule GRK2 inhibitors, including balanol, Takeda inhibitors, paroxetine and derivatives, M119 and gallein, peptides, RNA aptamers, Raf kinase inhibitory protein, and microRNAs, that can directly inhibit GRK2 kinase activity have been identified by different strategies. Paroxetine 70-80 G protein-coupled receptor kinase 2 Homo sapiens 15-19 29070696-8 2017 To investigate how these two warheads dictate selectivity, we determined the crystal structures of three of the indazole hybrid compounds (CCG224061, CCG257284, and CCG258748) in complex with GRK2-Gbetagamma Comparison of these structures with those of analogous benzodioxole-containing complexes confirmed that the indazole-paroxetine hybrids form stronger interactions with the hinge of the kinase but also stabilize a distinct conformation of the kinase domain of GRK2 compared with previous complexes with paroxetine analogs. Paroxetine 325-335 G protein-coupled receptor kinase 2 Homo sapiens 192-196 29070696-8 2017 To investigate how these two warheads dictate selectivity, we determined the crystal structures of three of the indazole hybrid compounds (CCG224061, CCG257284, and CCG258748) in complex with GRK2-Gbetagamma Comparison of these structures with those of analogous benzodioxole-containing complexes confirmed that the indazole-paroxetine hybrids form stronger interactions with the hinge of the kinase but also stabilize a distinct conformation of the kinase domain of GRK2 compared with previous complexes with paroxetine analogs. Paroxetine 510-520 G protein-coupled receptor kinase 2 Homo sapiens 192-196 28349925-6 2017 In vitro assay confirmed that paroxetine inhibits CX3CL1-induced T cell migration through blocking the activity of GRK2. Paroxetine 30-40 G protein-coupled receptor kinase 2 Homo sapiens 115-119 28323425-3 2017 The selective serotonin reuptake inhibitor, paroxetine, was previously identified as a GRK2 inhibitor. Paroxetine 44-54 G protein-coupled receptor kinase 2 Homo sapiens 87-91 24220010-1 2014 Recently we identified the serotonin reuptake inhibitor paroxetine as an inhibitor of G protein-coupled receptor kinase 2 (GRK2) that improves cardiac performance in live animals. Paroxetine 56-66 G protein-coupled receptor kinase 2 Homo sapiens 86-121 24220010-1 2014 Recently we identified the serotonin reuptake inhibitor paroxetine as an inhibitor of G protein-coupled receptor kinase 2 (GRK2) that improves cardiac performance in live animals. Paroxetine 56-66 G protein-coupled receptor kinase 2 Homo sapiens 123-127 24220010-2 2014 Paroxetine exhibits up to 50-fold selectivity for GRK2 versus other GRKs. Paroxetine 0-10 G protein-coupled receptor kinase 2 Homo sapiens 50-54 24220010-6 2014 Our results suggest that the selectivity of paroxetine for GRK2 largely reflects its lower affinity for adenine nucleotides. Paroxetine 44-54 G protein-coupled receptor kinase 2 Homo sapiens 59-63 24220010-8 2014 Next, we designed a benzolactam derivative of paroxetine that has optimized interactions with the hinge of the GRK2 kinase domain. Paroxetine 46-56 G protein-coupled receptor kinase 2 Homo sapiens 111-115 35155607-1 2021 Introduction: Paroxetine is a GRK2 inhibitor that has been widely used to treat depression and anxiety over the last few decades. Paroxetine 14-24 G protein-coupled receptor kinase 2 Homo sapiens 30-34 27222484-0 2017 Hypothesis: Paroxetine, a G Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor Reduces Morbidity and Mortality in Patients With Heart Failure. Paroxetine 12-22 G protein-coupled receptor kinase 2 Homo sapiens 26-61 27222484-0 2017 Hypothesis: Paroxetine, a G Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor Reduces Morbidity and Mortality in Patients With Heart Failure. Paroxetine 12-22 G protein-coupled receptor kinase 2 Homo sapiens 63-67 27222484-6 2017 Paroxetine is a selective serotonin reuptake inhibitor which was recently shown to have the ability to directly inhibit GRK2 both in vitro and in vivo. Paroxetine 0-10 G protein-coupled receptor kinase 2 Homo sapiens 120-124 27222484-7 2017 At physiologic temperatures, paroxetine inhibits GRK2-dependent phosphorylation of an activated G-protein-coupled receptor with a half maximal inhibitory concentration of 35 micromoles, a substantially greater affinity than for other G protein-coupled receptor kinases. Paroxetine 29-39 G protein-coupled receptor kinase 2 Homo sapiens 49-53 27999776-6 2016 It shows different strategies to inhibit GRK2 in HF in vivo (betaARK-ct gene therapy, treatment with gallein, and treatment with paroxetine) and in vitro (RNA aptamer, RKIP, and peptide-based inhibitors). Paroxetine 129-139 G protein-coupled receptor kinase 2 Homo sapiens 41-45 27695334-0 2016 Effects of paroxetine-mediated inhibition of GRK2 expression on depression and cardiovascular function in patients with myocardial infarction. Paroxetine 11-21 G protein-coupled receptor kinase 2 Homo sapiens 45-49 27695334-2 2016 Recent studies have identified paroxetine as a G protein-coupled receptor kinase-2 (GRK2) inhibitor capable of reversing cardiac dysfunction and remodeling in experimental models of acute myocardial infarction (AMI). Paroxetine 31-41 G protein-coupled receptor kinase 2 Homo sapiens 47-82 27695334-2 2016 Recent studies have identified paroxetine as a G protein-coupled receptor kinase-2 (GRK2) inhibitor capable of reversing cardiac dysfunction and remodeling in experimental models of acute myocardial infarction (AMI). Paroxetine 31-41 G protein-coupled receptor kinase 2 Homo sapiens 84-88 27695334-10 2016 Treatment of AMID patients with paroxetine significantly reduced the expression of GRK2, normalized the autonomic nervous system function, and improved cardiac performance. Paroxetine 32-42 G protein-coupled receptor kinase 2 Homo sapiens 83-87 27695334-12 2016 CONCLUSION: This study suggests that paroxetine is effective for improving cardiac function in patients with AMID and such effect correlates with GRK2 reduction. Paroxetine 37-47 G protein-coupled receptor kinase 2 Homo sapiens 146-150 25340299-2 2014 Previous studies have identified several compounds that selectively inhibit GRK2, such as paroxetine and balanol. Paroxetine 90-100 G protein-coupled receptor kinase 2 Homo sapiens 76-80 34259826-2 2021 Objective: To investigate the efficacy of paroxetine-mediated G-protein-coupled receptor kinase 2 inhibition to mitigate adverse left ventricular remodeling in patients presenting with acute myocardial infarction. Paroxetine 42-52 G protein-coupled receptor kinase 2 Homo sapiens 62-97 34386323-6 2021 CP-25 and GRK2 inhibitors (paroxetine or GSK180736A) inhibited the abnormal proliferation of FLS in RA patients and CIA rats by down-regulating GRK2 translocation to EP4 receptor. Paroxetine 27-37 G protein-coupled receptor kinase 2 Homo sapiens 10-14