Molecular Determinants for GPR55 Activity
Molecular Determinants for GPR55 Activity
批准号:
9891998
负责人:
MARY E ABOOD
金额:
$34.42万
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-05-15 至 2023-03-31
关键词:
AgonistAmino AcidsAreaBindingBiological AssayBone DevelopmentCNR1 geneCNR2 geneCannabinoidsCell LineCellsComplementDevelopmentDiseaseDrug ReceptorsDrug abuseExhibitsG-Protein-Coupled ReceptorsGPR35 geneGPR55 receptorGTP-Binding ProteinsGoalsHumanInstitutesLabelLibrariesLigandsMAP Kinase GeneMalignant NeoplasmsMediatingMedicalMetabolic DiseasesMolecularMolecular BankMutationNeurologicPathway interactionsPharmacotherapyPhysiologicalPlasmidsRadioactiveReceptor ActivationReporterSignal PathwaySignal TransductionSite-Directed MutagenesisStructureStructure-Activity RelationshipTechniquesTherapeuticUnited States National Institutes of Healthbasebeta-arrestinbonecheminformaticscross reactivitydesignhigh throughput screeninginflammatory paininterestlysophosphatidylinositolmolecular modelingmutantnanomolarnext generationpainful neuropathypreventprogramsradioligandreceptorrecruitrelease of sequestered calcium ion into cytoplasmresponsescaffoldtherapeutic targettooltrafficking
中文摘要
GPR55是一种溶血磷脂酰肌醇(LPI)敏感的g蛋白偶联受体(GPCR)
英文摘要
GPR55 is a lysophosphatidylinositol (LPI)-sensitive G-protein coupled receptor (GPCR) that recognizes a sub-
set of cannabinoid CB1 and CB2 ligands. The goal of the proposed project is to understand the functional
features of GPR55 that may define mechanisms of drug-receptor interactions relevant to physiological and
pathophysiological function, including drug abuse. GPR55 has been implicated in inflammatory pain,
neuropathic pain, metabolic disorder, bone and neurological development, and cancer, indicating the real
potential of GPR55 ligands as therapeutics. Each of these areas alone is medically important and each would
benefit by the use of selective agonists and antagonists to further studies. While selective agonists and
antagonists for GPR55 from a number of diverse scaffolds have been identified, no low nanomolar potency
ligands have been confirmed for this receptor, nor is there a radioligand developed to characterize binding. We
have recently identified the first set of GPR55 residues important for agonist signaling and for GPR55
activation. This information should aid in the rational design of next generation GPR55 ligands, using our
evolving molecular model. The goal of this proposal is to use structure-based design and cheminformatics
tools to develop structure-activity relationships for selected scaffolds, leading to the identification of low
nanomolar ligands that retain high receptor selectivity. We aim to discover nanomolar potency GPR55 ligands
using a combination of molecular modeling, chemoinformatics, high-throughput screening and site directed
mutagenesis. We will dissect the specific signaling pathways governing GPR55 activity as well as investigate
ligand bias.
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会议论文
Functional Role for GPR55 in the periaqueductal gray
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批准号:8827313
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项目类别:
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资助金额:$30.73万
-
财政年份:2014
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负责人:MARY E ABOOD
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依托单位:
Functional Role for GPR55 in the periaqueductal gray
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批准号:8695904
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项目类别:
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资助金额:$31.15万
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财政年份:2014
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负责人:MARY E ABOOD
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依托单位:
Optimization of High Selectivity Antagonist Hits for the GPR55 Receptor
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批准号:8479451
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项目类别:
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资助金额:$17.88万
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财政年份:2012
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负责人:MARY E ABOOD
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依托单位:
Optimization of High Selectivity Antagonist Hits for the GPR55 Receptor
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批准号:8400947
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项目类别:
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资助金额:$23.33万
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财政年份:2012
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负责人:MARY E ABOOD
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依托单位:
Pamoic acid analogues as potent GPR35 agoinsts inducing antinociception
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批准号:7782591
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项目类别:
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资助金额:$21.03万
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财政年份:2009
-
负责人:MARY E ABOOD
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依托单位:
Molecular Characterization of GPR35 and GPR55, Putative Cannabinoid Receptors
-
批准号:8065417
-
项目类别:
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资助金额:$30.89万
-
财政年份:2008
-
负责人:MARY E ABOOD
-
依托单位:
Molecular Characterization of GPR35 and GPR55, Putative Cannabinoid Receptors
-
批准号:7646619
-
项目类别:
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资助金额:$34.41万
-
财政年份:2008
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负责人:MARY E ABOOD
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依托单位:
Molecular Characterization of GPR35 and GPR55, Putative Cannabinoid Receptors
-
批准号:7446100
-
项目类别:
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资助金额:$32.03万
-
财政年份:2008
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负责人:MARY E ABOOD
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依托单位:
Molecular Characterization of GPR35 and GPR55, Putative Cannabinoid Receptors
-
批准号:7864275
-
项目类别:
-
资助金额:$31.77万
-
财政年份:2008
-
负责人:MARY E ABOOD
-
依托单位:
Molecular Characterization of GPR35 and GPR55, Putative Cannabinoid Receptors
-
批准号:8661145
-
项目类别:
-
资助金额:$29.84万
-
财政年份:2007
-
负责人:MARY E ABOOD
-
依托单位:
Molecular Characterization of GPR35 and GPR55, Putative Cannabinoid Receptors
-
批准号:8296972
-
项目类别:
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资助金额:$30.9万
-
财政年份:2007
-
负责人:MARY E ABOOD
-
依托单位:
Molecular Characterization of GPR35 and GPR55, Putative Cannabinoid Receptors
-
批准号:7249924
-
项目类别:
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资助金额:$39.8万
-
财政年份:2007
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负责人:MARY E ABOOD
-
依托单位:
CLONING AND CHARACTERIZATION OF CANNABINOID RECEPTORS
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批准号:7318581
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项目类别:
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资助金额:$13.01万
-
财政年份:2007
-
负责人:MARY E ABOOD
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依托单位:
Molecular Characterization of GPR35 and GPR55, Putative Cannabinoid Receptors
-
批准号:8446980
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项目类别:
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资助金额:$28.65万
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财政年份:2007
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负责人:MARY E ABOOD
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依托单位:
Anandamide Receptors: Role in Motor Neuron Protection
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批准号:6572272
-
项目类别:
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资助金额:$18.49万
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财政年份:2002
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负责人:MARY E ABOOD
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依托单位:
Anandamide Receptors: Role in Motor Neuron Protection
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批准号:6796993
-
项目类别:
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资助金额:$8.0万
-
财政年份:2002
-
负责人:MARY E ABOOD
-
依托单位:
Anandamide Receptors: Role in Motor Neuron Protection
-
批准号:6685937
-
项目类别:
-
资助金额:$18.49万
-
财政年份:2002
-
负责人:MARY E ABOOD
-
依托单位:
CLONING AND CHARACTERIZATION OF CANNABINOID RECEPTORS
-
批准号:6358468
-
项目类别:
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资助金额:$17.12万
-
财政年份:2000
-
负责人:MARY E ABOOD
-
依托单位:
CLONING AND CHARACTERIZATION OF CANNABINOID RECEPTORS
-
批准号:6218895
-
项目类别:
-
资助金额:$0.66万
-
财政年份:1999
-
负责人:MARY E ABOOD
-
依托单位:
CLONING AND CHARACTERIZATION OF CANNABINOID RECEPTORS
-
批准号:6103986
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项目类别:
-
资助金额:$0.66万
-
财政年份:1999
-
负责人:MARY E ABOOD
-
依托单位:
海外基金