Hsp90B in Bladder Cancer
Hsp90B in Bladder Cancer
批准号:
9922232
负责人:
Brian S J Blagg
金额:
$35.17万
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:
2018-05-08 至 2022-04-30
关键词:
AffinityAnimal ModelAntineoplastic AgentsBindingBinding SitesCardiotoxicityCellsClientClinicalClinical TrialsCollaborationsComplexCrystallizationDataDevelopmentDiseaseDoseDrug DesignDrug TargetingExhibitsFrequenciesGenerationsGoalsHSP 90 inhibitionHeat shock proteinsHeat-Shock Proteins 90Heat-Shock ResponseHepatotoxicityIn VitroIndividualLeadMAPK7 geneMalignant NeoplasmsMalignant neoplasm of urinary bladderMaximum Tolerated DoseMethodsMolecular ChaperonesMolecular ConformationN-terminalPathogenesisPathway interactionsPatientsPeripheral Nervous System DiseasesPharmaceutical PreparationsPharmacologyPlayProtein IsoformsProteinsProteomicsReportingResearch PersonnelRoleScheduleSignal TransductionStructureStudy modelsTimeToxic effectTranslatingValidationantitumor agentbaseclinical candidatedrug developmentin vivoinhibitor/antagonistinterestknock-downmolecular modelingmyelinationnanomolarneuropeptide Ynovel anticancer drugprotein degradationprotein foldingresearch clinical testingscaffoldside effect
中文摘要
非常需要开发治疗癌症的新方法。热休克蛋白90蛋白折叠机制
已经成为开发抗癌剂的重要目标。然而,Hsp90负责约300种蛋白质折叠底物的折叠,这可能导致不期望的靶向毒性,并且可能是许多在临床试验中失败的Hsp90靶向药物的原因。通过基于结构的方法,Hsp90的异构体选择性抑制剂已被鉴定,并显示出对特定癌症的良好选择性和亲和力。因此,本申请的目标是优化这种新的抑制性支架以获得更大的亲和力/功效,以评估特定Hsp90同种型在癌症中的作用,并验证这种同种型作为治疗膀胱癌的靶标。
英文摘要
The development of new methods to treat cancer is greatly needed. The Hsp90 protein folding machinery has
been the target of significant interest for the development of anti-cancer agents. However, Hsp90 is responsible for the folding of ~300 protein folding substrates, which may lead to undesired on-target toxicity and may be responsible for many of the Hsp90-targeted drugs that have failed in clinical trials. Through a structure-based approach, an isoform-selective inhibitor of Hsp90 has been identified and shown to exhibit good selectivity and affinity against particular cancers. Consequently, the goal of this application is to optimize this new inhibitory scaffold for great affinity/efficacy, to evaluate the role of a specific Hsp90 isoform in cancer, and to validate this isoform as a target for the treatment of bladder cancer.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Engineering the Next Generation of Safer Hsp90 Inhibitors
-
批准号:10587304
-
项目类别:
-
资助金额:$46.33万
-
财政年份:2023
-
负责人:Brian S J Blagg
-
依托单位:
Development and Evaluation of Purine and Coumarin Based Hsp90 Inhibitors
-
批准号:9514012
-
项目类别:
-
资助金额:$35.33万
-
财政年份:2018
-
负责人:Brian S J Blagg
-
依托单位:
Optimization and Investigation of Cruentaren A analogs
-
批准号:9902368
-
项目类别:
-
资助金额:$35.3万
-
财政年份:2018
-
负责人:Brian S J Blagg
-
依托单位:
Development and Evaluation of Purine and Coumarin Based Hsp90 Inhibitors
-
批准号:9600723
-
项目类别:
-
资助金额:$44.39万
-
财政年份:2018
-
负责人:Brian S J Blagg
-
依托单位:
Optimization and Investigation of Cruentaren A analogs
-
批准号:9454428
-
项目类别:
-
资助金额:$34.25万
-
财政年份:2018
-
负责人:Brian S J Blagg
-
依托单位:
Optimization and Investigation of Cruentaren A analogs
-
批准号:10078544
-
项目类别:
-
资助金额:$35.3万
-
财政年份:2018
-
负责人:Brian S J Blagg
-
依托单位:
New paradigms for Hsp90 inhibition
-
批准号:9762054
-
项目类别:
-
资助金额:$34.35万
-
财政年份:2017
-
负责人:Brian S J Blagg
-
依托单位:
New paradigms for Hsp90 inhibition
-
批准号:10000886
-
项目类别:
-
资助金额:$35.41万
-
财政年份:2017
-
负责人:Brian S J Blagg
-
依托单位:
New paradigms for Hsp90 inhibition
-
批准号:9379940
-
项目类别:
-
资助金额:$36.66万
-
财政年份:2017
-
负责人:Brian S J Blagg
-
依托单位:
Grp94-selective inhibitors to treat heredity glaucoma
-
批准号:8928624
-
项目类别:
-
资助金额:$41.23万
-
财政年份:2014
-
负责人:Brian S J Blagg
-
依托单位:
Grp94-selective inhibitors to treat heredity glaucoma
-
批准号:8785724
-
项目类别:
-
资助金额:$43.54万
-
财政年份:2014
-
负责人:Brian S J Blagg
-
依托单位:
Chaperone therapeutics for the treatment of DPN
-
批准号:8636503
-
项目类别:
-
资助金额:$31.44万
-
财政年份:2012
-
负责人:Brian S J Blagg
-
依托单位:
Chaperone therapeutics for the treatment of DPN
-
批准号:8297562
-
项目类别:
-
资助金额:$31.82万
-
财政年份:2012
-
负责人:Brian S J Blagg
-
依托单位:
Chaperone therapeutics for the treatment of DPN
-
批准号:8413041
-
项目类别:
-
资助金额:$30.68万
-
财政年份:2012
-
负责人:Brian S J Blagg
-
依托单位:
Development of Hsp90 inhibitors for the treatment of cancer
-
批准号:8456077
-
项目类别:
-
资助金额:$29.3万
-
财政年份:2012
-
负责人:Brian S J Blagg
-
依托单位:
Development of Hsp90 inhibitors for the treatment of cancer
-
批准号:8627592
-
项目类别:
-
资助金额:$30.29万
-
财政年份:2012
-
负责人:Brian S J Blagg
-
依托单位:
Chaperone therapeutics for the treatment of DPN
-
批准号:8824587
-
项目类别:
-
资助金额:$31.73万
-
财政年份:2012
-
负责人:Brian S J Blagg
-
依托单位:
COBRE: U KS: P1: ID OF HSP90 COCHAPERONES, IMMUNOPHILINS & PROTEINS
-
批准号:7720669
-
项目类别:
-
资助金额:$2.61万
-
财政年份:2008
-
负责人:Brian S J Blagg
-
依托单位:
HSP90 Inhibitors
-
批准号:8184864
-
项目类别:
-
资助金额:$24.43万
-
财政年份:2006
-
负责人:Brian S J Blagg
-
依托单位:
Hsp90 Inhibitors
-
批准号:7038182
-
项目类别:
-
资助金额:$25.32万
-
财政年份:2006
-
负责人:Brian S J Blagg
-
依托单位:
海外基金