Splice modulatory therapy for valley fever
谷热的剪接调节疗法
基本信息
- 批准号:10042570
- 负责人:
- 金额:$ 23.63万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-06-01 至 2022-05-31
- 项目状态:已结题
- 来源:
- 关键词:Acute Myelocytic LeukemiaAmphotericin BAntifungal AgentsArizonaAzolesBiologicalBiological MarkersBiologyCaliforniaCellsChemicalsClinicalCoccidioides immitisCoccidioides posadasiiCoccidioidomycosisCommunitiesDevelopmentDiagnosisDiseaseDrug InteractionsDustEvaluationEventFamilyFluconazoleFundingFutureGenesGoalsHumanIncidenceIndividualInfectionInvestigationLaboratoriesLeadLeftLifeMessenger RNAModernizationNatural ProductsOncogenicOutcomePathway interactionsPatientsPatternPharmaceutical ChemistryPharmaceutical PreparationsPlayPneumoniaPositioning AttributePrecipitationPreparationRNA SplicingReportingSeasonsSeriesSideSpliceosomesStructureSystemSystems BiologyTechniquesTestingTherapeuticTranslatingTranslationsUnited StatesWorkanaloganti-cancerbasecancer cellcombatdesert feverdesignflufungushigh rewardhigh risknew therapeutic targetnext generationnoveloutcome forecastpreclinical studyprogramsscaffoldside effectsmall moleculetherapeutic targettooltranscriptometranscriptomics
项目摘要
7. Project Summary.
Over the last five years, the incidence of coccidioidomycosis (Valley Fever) has been increasing at a
remarkable rate, making it a common cause of community-acquired pneumonia in the United States. While
largely under-diagnosed, the treatment of moderate to severe cases currently involves application of
amphotericin B or azole antifungals such as fluconazole, two drugs with indications complicated by severe
side-effects and drug interactions. Without other options, patients are often left untreated and with a poor
clinical prognosis. This is further complicated by the fact that many of the leads identified to combat
coccidioidomycosis to date target established antifungal targets, without consideration of the efficacy of
targeting these pathways in their fungal hosts. Over the last decade, our team has focused on the development
of small molecule modulators of human splicing. We have learned how the unique interplay between systems-
wide and mechanism-based understanding plays a key role in developing viable therapeutic leads for
oncogenic diseases. This program explores the translation splice modulators as next-generation treatments for
coccidioidomycosis by uniting medicinal chemical optimization efforts with gene and transcriptome-wide tools.
This high-risk / high-reward program unites chemical biology with an active program in medicinal chemistry to
evaluate, test and validate the spliceosome-targeting small molecules for the treatment of severe
coccidioidomycosis.
7. 项目总结。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Michael D. Burkart其他文献
Data from mass spectrometry, NMR spectra, GC–MS of fatty acid esters produced by <em>Lasiodiplodia theobromae</em>
- DOI:
10.1016/j.dib.2016.05.003 - 发表时间:
2016-09-01 - 期刊:
- 影响因子:
- 作者:
Carla C. Uranga;Joris Beld;Anthony Mrse;Iván Córdova-Guerrero;Michael D. Burkart;Rufina Hernández-Martínez - 通讯作者:
Rufina Hernández-Martínez
Reversal of malignant ADAR1 splice isoform switching with Rebecsinib
用 Rebecsinib 逆转恶性 ADAR1 剪接异构体转换
- DOI:
10.1016/j.stem.2023.01.008 - 发表时间:
2023-03-02 - 期刊:
- 影响因子:20.400
- 作者:
Leslie A. Crews;Wenxue Ma;Luisa Ladel;Jessica Pham;Larisa Balaian;S. Kathleen Steel;Phoebe K. Mondala;Raymond H. Diep;Christina N. Wu;Cayla N. Mason;Inge van der Werf;Isabelle Oliver;Eduardo Reynoso;Gabriel Pineda;Thomas C. Whisenant;Peggy Wentworth;James J. La Clair;Qingfei Jiang;Michael D. Burkart;Catriona H.M. Jamieson - 通讯作者:
Catriona H.M. Jamieson
Gating mechanism of elongating β-ketoacyl-ACP synthases
延伸β-酮脂酰-ACP 合酶的门控机制
- DOI:
10.1038/s41467-020-15455-x - 发表时间:
2020-04-07 - 期刊:
- 影响因子:15.700
- 作者:
Jeffrey T. Mindrebo;Ashay Patel;Woojoo E. Kim;Tony D. Davis;Aochiu Chen;Thomas G. Bartholow;James J. La Clair;J. Andrew McCammon;Joseph P. Noel;Michael D. Burkart - 通讯作者:
Michael D. Burkart
The Complete Characterization of a Trapped ACYL Carrier Protein-Ketosynthase Complex
- DOI:
10.1016/j.bpj.2019.11.1114 - 发表时间:
2020-02-07 - 期刊:
- 影响因子:
- 作者:
Jeffrey T. Mindrebo;Laetitia E. Misson;Ashay Patel;Katia Charov;Joseph P. Noel;Michael D. Burkart - 通讯作者:
Michael D. Burkart
Crosslinking intermodular condensation in non-ribosomal peptide biosynthesis
非核糖体肽生物合成中的交联模块间缩合
- DOI:
10.1038/s41586-024-08306-y - 发表时间:
2024-12-11 - 期刊:
- 影响因子:48.500
- 作者:
Graham W. Heberlig;James J. La Clair;Michael D. Burkart - 通讯作者:
Michael D. Burkart
Michael D. Burkart的其他文献
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{{ truncateString('Michael D. Burkart', 18)}}的其他基金
Targeting Metal-Dependent Epigenetic Modulators via MetalloPROTACs
通过 MetalloPROTAC 靶向金属依赖性表观遗传调节剂
- 批准号:
10722294 - 财政年份:2023
- 资助金额:
$ 23.63万 - 项目类别:
Enabling synthetic biology through single cell functional genomics
通过单细胞功能基因组学实现合成生物学
- 批准号:
10556421 - 财政年份:2022
- 资助金额:
$ 23.63万 - 项目类别:
Targeting protein-protein interactions as drug targets
将蛋白质-蛋白质相互作用作为药物靶点
- 批准号:
10306398 - 财政年份:2020
- 资助金额:
$ 23.63万 - 项目类别:
Chemical Biology Interfaces at UC San Diego
加州大学圣地亚哥分校的化学生物学接口
- 批准号:
9064164 - 财政年份:2015
- 资助金额:
$ 23.63万 - 项目类别:
Chemical Biology Interfaces at UC San Diego
加州大学圣地亚哥分校的化学生物学接口
- 批准号:
8794193 - 财政年份:2015
- 资助金额:
$ 23.63万 - 项目类别:
Protein-Protein Interactions in Natural Product Biosynthesis
天然产物生物合成中的蛋白质-蛋白质相互作用
- 批准号:
10249686 - 财政年份:2012
- 资助金额:
$ 23.63万 - 项目类别:
Protein-Protein Interactions in Natural Product Biosynthesis
天然产物生物合成中的蛋白质-蛋白质相互作用
- 批准号:
10548747 - 财政年份:2012
- 资助金额:
$ 23.63万 - 项目类别:
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