Novel Analgesics for the Treatment of Bone Cancer Pain

描述（由申请人提供）：疼痛是癌症患者最常见的症状，骨转移是癌症相关疼痛的最常见来源之一。在世界卫生组织（WHO）制定的三步指南中，非阿片类镇痛药（对乙酰氨基酚和NSAID）是对抗癌症疼痛的第一步。在步骤2中，当用非阿片类药物不能实现疼痛缓解时，协同阿片类药物/非阿片类药物组合（例如，可待因+对乙酰氨基酚）。因此，对乙酰氨基酚是一种广泛使用的有效治疗骨癌相关疼痛的药物。然而，人们已经认识到，即使在治疗剂量下，对乙酰氨基酚也会引起肝毒性。癌症患者暴露于多种化疗药物，这些化疗药物使肝功能达到极限，因此特别容易受到对乙酰氨基酚诱导的肝毒性的影响。因此，一种不消耗谷胱甘肽储存的对乙酰氨基酚类镇痛剂将增加第1步和第2步药物治疗癌症相关疼痛的能力，并填补癌症患者可用选择的重要空白。我们目前正在探索一系列新的和专有的对乙酰氨基酚衍生物，其中先导化合物（SCP-1）具有良好的口服疗效，与阿片类药物协同作用，似乎可以克服对乙酰氨基酚的肝毒性缺点。在这个I期SBIR项目中，我们将确定使用这种独特的化合物作为骨癌疼痛的第1阶段和第2阶段治疗的可行性。

DESCRIPTION (provided by applicant): Pain is the most prevalent symptom in cancer patients, and bone metastasis is one of the most common sources of cancer-related pain. In the 3-step guidelines established by the World Health Organization (WHO) non-opioid analgesics (acetaminophen and NSAIDs) are the first step against cancer pain. In step 2, when pain relief is not achieved with non-opioid medications, synergistic opioid/non-opioid combinations (e.g., codeine + acetaminophen) are used. Thus, acetaminophen is a heavily used efficacious treatment for bone cancer-related pain. However, it has been recognized that even at therapeutic doses acetaminophen causes liver toxicity. Cancer patients are exposed to a multitude of chemotherapeutics that tax liver function to the limit, and thus are particularly susceptible to acetaminophen-induced liver toxicity. Therefore, an acetaminophen-like analgesic that does not deplete glutathione stores would increase the ability to treat cancer-related pain with Step 1 and Step 2 medications, and fill an important void in the options available to cancer patients. We are currently exploring a series of new and proprietary derivatives of acetaminophen, in which the lead compound (SCP-1) has good oral efficacy that is synergistic with opioids, and appears to overcome the hepatotoxic shortcomings of acetaminophen. Under this Phase I SBIR project, we will determine the feasibility of using this unique compound as stage 1 and stage 2 treatments of bone cancer pain.