A new class of non-opioid analgesics for use in chronic pain management

 描述（由申请人提供）：急性和慢性疼痛给社会带来了巨大的负担，这不仅是因为相关的人类痛苦，而且还因为医疗费用、生产力损失和残疾支付，据估计，仅在美国每年就高达6500亿美元。目前的疼痛治疗受到疗效有限和急性或长期副作用的阻碍。 对乙酰氨基酚是一种重要的药物在疼痛的管理;然而，过量（这是很常见的）可导致肝损伤，随后肝衰竭，甚至死亡。一种安全的非肝毒性药物，与对乙酰氨基酚相比具有相同或更高的疗效，将是治疗疼痛的突破性新产品。 Kalyra Pharmaceuticals利用我们的专有生物电子等排体工具箱合成了许多结构相关的对乙酰氨基酚类似物，并发现了不形成有毒代谢物的新型高效镇痛化合物。随着概念的证明，这些类似物的进一步开发是这一直接进入II期提案的主题，具体目标概述如下：II期：疼痛新治疗方法的非临床开发目标1。疗效和体内药理学目的的进一步表征2. ADMET，其他药理学和初步毒理学目标3。药代动力学研究，以确认安全性目标4的第二种属选择。支持IND申报的非临床毒理学研究在完成本提案中概述的IND启动研究后，我们预计将向FDA提交IND申报，以开始人体临床试验，开发一种新型、安全、有效和非成瘾性的疼痛管理新疗法。

 DESCRIPTION (provided by applicant): Acute and chronic pain imposes a tremendous burden on society, not only because of the associated human suffering, but also the cost of medical treatment, loss of productivity and disability payments, which has been estimated to be up to $650 billion per year in the USA alone. Current treatments for pain are hampered by limited efficacy and acute or long-term side effects. Acetaminophen is an important drug in the management of pain; however, overdose (which is quite common) can lead to liver damage, subsequent liver failure, and even death. A safe non-liver toxic drug, with equal or improved efficacy compared to acetaminophen, would be a ground breaking new product for the treatment of pain. Kalyra Pharmaceuticals has synthesized a number of structurally related acetaminophen analogs, utilizing our toolbox of proprietary bioisosteres, and discovered new highly potent analgesic compounds that do not form a toxic metabolite. With proof of concept in hand, further development of these analogues is the subject of this direct to Phase II proposal, via the Specific Aims outlined below: Phase II: Non-Clinical Development of a New Treatment for Pain Aim 1. Further Characterization of Efficacy and In Vivo Pharmacology Aim 2. ADMET, Additional Pharmacology and Preliminary Toxicology Aim 3. Pharmacokinetic Studies to Confirm Second Species Selection for Safety Aim 4. Non-Clinical Toxicology Studies in Support of Filing of an IND After completion of the IND-enabling studies outlined in this proposal, we anticipate the filing of an IND with the FDA to begin human clinical trials for the development of a novel, safe, effective and non-addictive new treatment for the management of pain.