Chemical Methods for Ferrous Iron Dependent Drug Delivery
二价铁依赖性药物递送的化学方法
基本信息
- 批准号:8577786
- 负责人:
- 金额:$ 34.71万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-05-29 至 2018-04-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAnimal ModelAnimalsAntimalarialsArtemisininsBiologicalBloodCatabolismCellsCessation of lifeChemicalsChildCombined Modality TherapyComplexCysteineDiseaseDoseDrug CombinationsDrug Delivery SystemsDrug KineticsDrug resistanceEffectivenessEvaluationEventExposure toGenerationsGoalsHeme IronHemoglobinHistone Deacetylase InhibitorHomeostasisHourIn SituIn VitroInfectionIronLifeLiverMalariaMetabolicMethodsMorbidity - disease rateMusOralOxidation-ReductionParasitesPathologyPathway interactionsPatientsPeroxidesPharmaceutical ChemistryPharmaceutical PreparationsPharmacodynamicsPharmacologyPlasmodium bergheiPlasmodium falciparumPlasmodium vivaxPrimaquinePropertyReactionResearchResistanceSafetySideStagingSystemTechnologyTherapeuticTissuesWorkanalogartemisininedesigndisease diagnosisdrug discoveryfunctional grouphuman diseaseimprovedin vitro activityin vivoinhibitor/antagonistmortalitynext generationnovel strategiespublic health relevancesmall moleculestandard of caretargeted deliverytherapeutic target
项目摘要
DESCRIPTION (provided by applicant): Hemoglobin-digesting parasites, including the malaria parasites Plasmodium falciparum and Plasmodium vivax generate significant concentrations of free ferrous iron heme, which is formed as a result of hemoglobin catabolism by the parasite. These reactive forms of iron present an opportunity for iron(II)-targeted drug delivery, since free
forms of ferrous iron are exceedingly rare in healthy tissue and cells. We have developed and validated in animals an iron(II)-targeted drug delivery technology for delivery of therapeutics to the malaria parasites, or more generally, to any biological compartment containing unbound ferrous iron. Drug delivery strategies have scarcely been investigated in anti-parasitic therapy but these approaches have the potential to target parasites selectively, protecting the patient from exposure to active drug species and possibly allowing the safe use of a broader range of therapeutics. Our delivery systems are comprised of a 1,2,4-trioxolane ring system as an iron(II)-sensing 'trigger' moiety and a 'traceless' linker to which the partner drug is attached an ultimately released via a ?-elimination reaction. The chemical design is such that drugs from a wide swath of chemical and therapeutic target space can in principle be delivered using the approach. In preliminary work, we synthesized prototypical delivery systems and demonstrated the iron(II)-dependent and parasite-selective delivery of a cysteine inhibitor to Plasmodium berghei parasites in infected mice. The goals of the proposed research are to evaluate in animals a new generation of more drug-like delivery systems, and to identify partner drug species that are optimally suited for this new approach to antimalarial therapy.
描述(由申请人提供):消化血红蛋白的寄生虫,包括疟疾寄生虫恶性疟原虫和间日疟原虫,产生高浓度的游离亚铁铁血红素,这是寄生虫血红蛋白分解代谢的结果。这些活性形式的铁为铁(II)靶向药物递送提供了机会,因为它们是免费的
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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Adam R Renslo其他文献
Drug discovery and development for neglected parasitic diseases
被忽视的寄生虫病的药物发现和开发
- DOI:
10.1038/nchembio837 - 发表时间:
2006-12-01 - 期刊:
- 影响因子:13.700
- 作者:
Adam R Renslo;James H McKerrow - 通讯作者:
James H McKerrow
Adam R Renslo的其他文献
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{{ truncateString('Adam R Renslo', 18)}}的其他基金
Chemical Methods for Ferrous Iron Dependent Drug Delivery
二价铁依赖性药物递送的化学方法
- 批准号:
8843775 - 财政年份:2013
- 资助金额:
$ 34.71万 - 项目类别:
Chemical Methods for Ferrous Iron Dependent Drug Delivery
二价铁依赖性药物递送的化学方法
- 批准号:
8666719 - 财政年份:2013
- 资助金额:
$ 34.71万 - 项目类别:
Chemical Methods for Ferrous Iron Dependent Drug Delivery
二价铁依赖性药物递送的化学方法
- 批准号:
10223130 - 财政年份:2013
- 资助金额:
$ 34.71万 - 项目类别:
Chemical Methods for Ferrous Iron Dependent Drug Delivery
二价铁依赖性药物递送的化学方法
- 批准号:
10466820 - 财政年份:2013
- 资助金额:
$ 34.71万 - 项目类别:
Identification of Anti-HIV Lead Compounds Targeting Rev
鉴定针对 Rev 的抗 HIV 先导化合物
- 批准号:
7622185 - 财政年份:2009
- 资助金额:
$ 34.71万 - 项目类别:
Identification of Anti-HIV Lead Compounds Targeting Rev
鉴定针对 Rev 的抗 HIV 先导化合物
- 批准号:
7922936 - 财政年份:2009
- 资助金额:
$ 34.71万 - 项目类别:
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