Development of PAR2 Antagonists for Control of Asthma
Development of PAR2 Antagonists for Control of Asthma
批准号:
9592081
负责人:
Scott Boitano
金额:
$22.72万
依托单位:
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:
2018-06-01 至 2020-05-31
关键词:
AcuteAddressAdultAdverse effectsAffectAllergensAlternariaAnimal ModelArrestinsAsthmaBenignCellsChildChronicCollaborationsCompetitive BindingDataDevelopmentDictyopteraDinoprostoneDiseaseEnvironmental ExposureEpithelialEpithelial CellsExploratory/Developmental GrantExposure toExtrinsic asthmaG-Protein-Coupled ReceptorsGPR17 geneGTP-Binding ProteinsHumanHyperplasiaImmune responseIn VitroIndustrializationInflammationInflammatoryKnock-outKnockout MiceLaboratoriesLibrariesLung diseasesMAP Kinase GeneMeasuresMetabolismModelingMucous body substanceMusPAR-2 ReceptorPainPathway interactionsPatientsPeptide HydrolasesPerformancePharmaceutical ChemistryPharmaceutical PreparationsPharmacologyPharmacotherapyPhysiologicalPollenPopulationPre-Clinical ModelPrevalenceProstaglandin ProductionReportingRespiratory Signs and SymptomsRoleSignal TransductionSymptomsSyndromeTestingTherapeuticToxic effectabsorptionairway hyperresponsivenessarrestin 2clinically relevantcytokinedrug developmentdrug discoveryexperimental studyfungusimprovedin vivoin vivo Modelinflammatory painmouse modelneutralizing antibodynew therapeutic targetnovelnovel strategiesnovel therapeuticspeptidomimeticspre-clinicalpreclinical evaluationprotective effectpyroglyphidrecruitresponsescreeningsmall molecule
中文摘要
项目摘要
英文摘要
Project Abstract
Allergic asthma is increasing in prevalence and triggered by specific environmental exposures. Over the
past several decades asthma treatments have been largely unchanged and it is an unfortunate reality that
asthma remains uncontrolled in more than half the patients receiving standard asthma medication. Unlike more
benign allergens such as pollens, asthma-associated allergens (asthmagens; e.g., certain fungi, cockroaches,
and dust mites) have protease activity. Asthmagen proteases provide multiple mechanisms for increased
allergen activity including the direct activation of the G protein-coupled receptor (GPCR), Protease-activated
receptor-2 (PAR2). In mouse models, knockout of PAR2 significantly reduces asthma allergen-induced asthma
symptoms. Recent reports have shown that PAR2 neutralizing antibodies can also effectively reduce allergen-
induced asthma symptoms. Taken together, PAR2 provides a novel target for drug discovery in the control of
allergic asthma. We have recently developed a potent and specific PAR2 antagonist shown to block airway
epithelial PAR2 signaling in vitro and block PAR2-associated pain response in vivo. Preliminary data from our
laboratory suggests that C391 can effectively reduce allergen-induced asthma in conventional mouse models.
In this application we propose to optimize C391 for pharmacological control of the development of allergic
asthma in highly relevant in vivo models. Optimization includes reduced size, improved absorption, distribution,
metabolism and toxicity performance as well as improved in vivo performance as measured by asthma
symptom control in highly relevant pre-clinical models. The completion of these aims will provide a large pre-
clinical step toward the development of a new class of asthma therapeutics.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Development of small molecule Protease-activated-receptor-2 antagonists as oral asthma therapeutics
-
批准号:10766584
-
项目类别:
-
资助金额:$30.0万
-
财政年份:2023
-
负责人:Scott Boitano
-
依托单位:
Development of SP-A Derived Peptidomimetics for the Treatment of Asthma - Phase II
-
批准号:10551972
-
项目类别:
-
资助金额:$195.56万
-
财政年份:2022
-
负责人:Scott Boitano
-
依托单位:
Development of SP-A Derived Peptidomimetics for the Treatment of Asthma - Phase II
-
批准号:10708853
-
项目类别:
-
资助金额:$147.82万
-
财政年份:2022
-
负责人:Scott Boitano
-
依托单位:
Development of Small Molecule Antagonists of PAR-2 for treatment of asthma
-
批准号:10326155
-
项目类别:
-
资助金额:$28.34万
-
财政年份:2021
-
负责人:Scott Boitano
-
依托单位:
Development of surfactant protein A-derived peptidomimetics for the treatment of asthma
-
批准号:10019073
-
项目类别:
-
资助金额:$21.49万
-
财政年份:2020
-
负责人:Scott Boitano
-
依托单位:
Protease Activated Receptor Type 2 Targeting for Migraine Pain
-
批准号:10161867
-
项目类别:
-
资助金额:$48.11万
-
财政年份:2017
-
负责人:Scott Boitano
-
依托单位:
Protease Activated Receptor Type 2 Targeting for Migraine Pain
-
批准号:9397091
-
项目类别:
-
资助金额:$49.43万
-
财政年份:2017
-
负责人:Scott Boitano
-
依托单位:
Protease Activated Receptor Type 2 Targeting for Migraine Pain
-
批准号:9927698
-
项目类别:
-
资助金额:$48.11万
-
财政年份:2017
-
负责人:Scott Boitano
-
依托单位:
Protease Activated Receptor Type 2 Targeting for Migraine Pain
-
批准号:9293876
-
项目类别:
-
资助金额:$43.92万
-
财政年份:2016
-
负责人:Scott Boitano
-
依托单位:
PAR2 targeted drug discovery for the treatment of pain
-
批准号:8543773
-
项目类别:
-
资助金额:$31.64万
-
财政年份:2011
-
负责人:Scott Boitano
-
依托单位:
PAR2 targeted drug discovery for the treatment of pain
-
批准号:8320115
-
项目类别:
-
资助金额:$32.8万
-
财政年份:2011
-
负责人:Scott Boitano
-
依托单位:
PAR2 targeted drug discovery for the treatment of pain
-
批准号:8723906
-
项目类别:
-
资助金额:$32.45万
-
财政年份:2011
-
负责人:Scott Boitano
-
依托单位:
PAR2 targeted drug discovery for the treatment of pain
-
批准号:8237519
-
项目类别:
-
资助金额:$32.81万
-
财政年份:2011
-
负责人:Scott Boitano
-
依托单位:
International Gap Junction Conference 2009
-
批准号:7750265
-
项目类别:
-
资助金额:$1.73万
-
财政年份:2009
-
负责人:Scott Boitano
-
依托单位:
MODELING AIRWAY RESPONSE TO BORDETELLA SP INFECTION
-
批准号:6499041
-
项目类别:
-
资助金额:$17.3万
-
财政年份:2001
-
负责人:Scott Boitano
-
依托单位:
MODELING AIRWAY RESPONSE TO BORDETELLA SP INFECTION
-
批准号:6629059
-
项目类别:
-
资助金额:$18.47万
-
财政年份:2001
-
负责人:Scott Boitano
-
依托单位:
MODELING AIRWAY RESPONSE TO BORDETELLA SP INFECTION
-
批准号:6262696
-
项目类别:
-
资助金额:$17.22万
-
财政年份:2001
-
负责人:Scott Boitano
-
依托单位:
CA2+, GAP JUNCTIONS & COMMUNICATION IN ALVEOLAR II CELLS
-
批准号:6085049
-
项目类别:
-
资助金额:$13.54万
-
财政年份:2000
-
负责人:Scott Boitano
-
依托单位:
海外基金