Cancer radiotherapy: sensitization by inhibitors of PAR*

描述（由申请人提供）： 核酶聚（ADP-核糖）合成酶（PARP）的活化已经被证实是一种重要的酶。 涉及从辐射诱导的细胞损伤中恢复的过程。 因此，PARP的抑制剂或缺乏PARP的细胞表现出 增强其辐射敏感性。 这个原则 PARP抑制的放射增敏作用可用于 用于癌症治疗的新型放射增敏剂的开发。 的 申请人正在开发一系列新颖的专利PARP抑制剂， 高效能，良好的水溶性和最佳的细胞渗透 特色 本申请的目标由以下支持： 初步数据，是为了证实申请人的专有的，新的PARP 抑制剂在体内作为有效的放射增敏剂，并选择一个铅 进一步临床前开发的候选药物（即毒性和安全性 研究）。 本申请的结果将允许申请 第2阶段供资支持：完成临床前药物测试 （额外的高级毒性测定、病理学、稳定性， 药代动力学），准备向FDA提交的研究药物申请， 以及一、二期临床试验。 拟定商业应用： 一种有效的治疗药物的年预期收入， 光是在美国放射治疗就超过一亿美元。

DESCRIPTION (provided by applicant): Activation of the nuclear enzyme poly (ADP-ribose) synthetase (PARP) has been implicated in the process of recovery from radiation induced cell injury. Consequently, inhibitors of PARP or cells deficient from PARP exhibit enhancements in their radiation sensitivity. The principle of this radiosensitizing effect of PARP inhibition can be exploited for the development of novel radiosensitizing agents for cancer therapy. The applicants are developing a series of novel, proprietary PARP inhibitors, with a high potency, good water-solubility and optimal cell penetration characteristics. The goal of the present application, supported by preliminary data, is to confirm that the applicants' proprietary, novel PARP inhibitors act as potent radiosensitizers in vivo, and to select a lead candidate for further preclinical development (i.e. toxicity and safety studies). The results of the present application will permit application for Phase 2 funding to support: completion of pre-clinical pharmaceutical testing (additional advanced toxicity determinations, pathology, stability, pharmacokinetics), preparation of investigational drug application to the FDA, and a Phase I and II clinical trials. PROPOSED COMMERCIAL APPLICATION: The annual anticipated revenues for an effective therapeutic to safely enhance radiation therapy is over $100 million in the US alone.