Cancer radiotherapy: sensitization by inhibitors of PAR*

描述(由申请人提供)： 核酶多(ADP-核糖)合成酶(PARP)的激活 参与辐射所致细胞损伤的恢复过程。 因此，PARP的抑制剂或缺乏PARP的细胞表现出 增强了它们的辐射敏感性。这样做的原则是 PARP抑制可发挥放射增敏作用 用于癌症治疗的新型放射增敏剂的开发。这个 申请者正在开发一系列新颖的专有PARP抑制剂， 高效性、良好的水溶性和最佳的电池渗透性 特点。本申请的目标由 初步数据，是为了确认申请人的专有、新颖的PARP 在体内，抑制剂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者(即毒性和安全性 研究)。本申请的结果将允许申请 第二阶段资金支持：完成临床前药物测试 (其他高级毒性测定、病理学、稳定性、 药代动力学)，准备向FDA提交研究药物申请， 以及I期和II期临床试验。 建议的商业应用： 有效治疗以安全增强的年度预期收入 仅在美国，放射治疗的费用就超过1亿美元。

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.