IND-Enabling Preclinical Development of a New Radiomitigator
IND 促进新型放射缓解剂的临床前开发
基本信息
- 批准号:9280853
- 负责人:
- 金额:$ 43.64万
- 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:2013-06-15 至 2020-05-31
- 项目状态:已结题
- 来源:
- 关键词:AgonistBenzoic AcidsBloodBone MarrowBudgetsChemistryCost SharingDataDevelopmentDevelopment PlansDevicesDoseDrug KineticsDrug TargetingEdg4 ProteinEmergency SituationExplosionFDA approvedFeedbackFukushimaG-Protein-Coupled ReceptorsGoalsGrantHalf-LifeHematopoieticHourIn VitroIntellectual PropertyIsomerismLeadLengthLigandsLipidsLysophosphatidic Acid ReceptorsMacaca mulattaMethodsMolecularMusNuclearNuclear AccidentsPartition CoefficientPharmaceutical ChemistryPharmaceutical PreparationsPlacebosPropertyRadiationRadiation InjuriesRadiation ToxicityRadiation exposureRegimenResearchResourcesSpecificityStructureTennesseeTerrorismTherapeuticToxic effectToxicologyUniversitiesWhole-Body IrradiationWorkanaloganimal rulebasedesigndrug developmentefficacy studyexperiencegastrointestinalimprovedin vivoindustry partnerinorganic phosphateirradiationlysophosphatidic acidmeetingsmolecular massmortalitymouse modelphosphonatepreclinical developmentpreclinical evaluationpublic health relevancereceptorscaffoldsmall moleculespecific biomarkerssuccessthiophosphatetreatment group
项目摘要
DESCRIPTION (provided by applicant): The overall objective of this project is to conduct IND-enabling drug development of a new small molecule radiomitigator based on the RP239 lead structure thru a partnership between the University of Tennessee and RxBio. Inc. This objective originates from a decade-long radiomitigator research that identified and validated the lysophosphatidic acid (LPA) G protein-coupled receptor (GPCR) subtype 2 (LPA2) as a therapeutic drug target for radiomitigation. RP239 is a specific small molecule agonist of LPA2. This proposal builds on our past experience and success developing octadecenyl thiophosphate (OTP) as a radiomitigator of the gastrointestinal acute radiation syndrome (GI-ARS). OTP licensed to RxBio Inc. was entered into the FDA regulatory pipeline under the sponsorship of BARDA in 2011.    
RP239 when applied +24h after LD90/8-10 (16.59 Gy) partial-body γ-irradiation with 5% bone marrow shielding reduced mortality of mice from the gastrointestinal acute radiation syndrome (ARS) by 72% (11/14 survival vs. 1/14 in placebo). RP239 and its analogs were also effective in reducing mortality due to the hematopoietic ARS. Importantly, when treatment was delayed to +48h post-total body irradiation, 50% of the mice survived in the RP239 treatment group compared to 21% in the placebo group. Its drug-like properties, combined with its specificity to the LPA2 receptor and lack of toxicity at therapeutic doses lead us to hypothesize that RP239 should be further evaluated as a potent radiomitigator of the mixed ARS elicited by high-levels of radiation. Our unique resources and experience with the development of OTP provide us with qualifications to take the RP239 lead on a development path that will qualify this new radiomitigator for fast tracking by the FDA under the animal rule.
描述(由申请人提供):本项目的总体目标是通过田纳西大学和RxBio之间的合作,对基于RP 239先导结构的新型小分子放射性激动剂进行IND使能药物开发。Inc.这一目标源于一项长达十年的放射性激动剂研究,该研究确定并验证了溶血磷脂酸(LPA)G蛋白偶联受体(GPCR)亚型2(LPA 2)作为放射性激动的治疗药物靶点。RP 239是LPA 2的特异性小分子激动剂。这项建议建立在我们过去的经验和成功开发十八烯基硫代磷酸盐(OTP)作为胃肠急性放射综合征(GI-ARS)的放射性拮抗剂。OTP授权给RxBio Inc.在巴尔达的赞助下,于2011年进入FDA监管渠道。    
在LD 90/8-10(16.59戈伊)局部γ射线照射后+24小时,使用5%骨髓屏蔽,RP 239使胃肠道急性放射综合征(ARS)小鼠的死亡率降低了72%(11/14存活vs.安慰剂组1/14)。RP 239及其类似物也有效降低了由于造血ARS引起的死亡率。重要的是,当治疗延迟至全身照射后+48小时时,RP 239治疗组中50%的小鼠存活,而安慰剂组中为21%。其药物样性质,结合其对LPA 2受体的特异性和在治疗剂量下缺乏毒性,使我们假设RP 239应进一步评估为高水平辐射引起的混合ARS的有效放射性引发剂。我们在OTP开发方面的独特资源和经验为我们提供了在开发道路上领先RP 239的资格,这将使这种新的放射性激动剂有资格获得FDA根据动物规则的快速跟踪。
项目成果
期刊论文数量(0)
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{{ truncateString('GABOR J TIGYI', 18)}}的其他基金
IND-enabling development of Radioprotectin 1: a dual GI/HE radiation mitigator
Radioprotectin 1 的 IND 开发:双重 GI/HE 辐射缓解剂
- 批准号:10794519 
- 财政年份:2023
- 资助金额:$ 43.64万 
- 项目类别:
Radiobiology Research Suite Expansion of the TriMetis GLP Vivarium at UTHSC
UTHSC 的 TriMetis GLP Vivarium 放射生物学研究套件扩建
- 批准号:10374310 
- 财政年份:2021
- 资助金额:$ 43.64万 
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IND-enabling development of Radioprotectin 1: a dual GI/HE radiation mitigator
Radioprotectin 1 的 IND 开发:双重 GI/HE 辐射缓解剂
- 批准号:10401460 
- 财政年份:2020
- 资助金额:$ 43.64万 
- 项目类别:
IND-enabling development of Radioprotectin 1: a dual GI/HE radiation mitigator
Radioprotectin 1 的 IND 开发:双重 GI/HE 辐射缓解剂
- 批准号:10845827 
- 财政年份:2020
- 资助金额:$ 43.64万 
- 项目类别:
IND-enabling development of Radioprotectin 1: a dual GI/HE radiation mitigator
Radioprotectin 1 的 IND 开发:双重 GI/HE 辐射缓解剂
- 批准号:10194368 
- 财政年份:2020
- 资助金额:$ 43.64万 
- 项目类别:
IND-Enabling Preclinical Development of a New Radiomitigator
IND 促进新型放射缓解剂的临床前开发
- 批准号:9064077 
- 财政年份:2013
- 资助金额:$ 43.64万 
- 项目类别:
IND-Enabling Preclinical Development of a New Radiomitigator
IND 促进新型放射缓解剂的临床前开发
- 批准号:8842923 
- 财政年份:2013
- 资助金额:$ 43.64万 
- 项目类别:
Novel Radiomitigators Targeting LPA Receptors
针对 LPA 受体的新型放射缓解剂
- 批准号:8760294 
- 财政年份:2012
- 资助金额:$ 43.64万 
- 项目类别:
Novel Radiomitigators Targeting LPA Receptors
针对 LPA 受体的新型放射缓解剂
- 批准号:8963438 
- 财政年份:2012
- 资助金额:$ 43.64万 
- 项目类别:
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