Discovery of Novel Pharmaceutical Agents for Skeletal Muscle Atrophy

项目摘要/摘要 仅在美国，骨骼肌萎缩就会降低数千万人的健康和生活质量。 肌肉萎缩的常见原因(通常在同一患者中共存)包括衰老、营养不良、 肌肉停用，危重疾病，某些药物，以及包括癌症在内的一系列慢性病， 心力衰竭、慢性阻塞性肺病、糖尿病、肾功能衰竭、肝硬变、类风湿性关节炎和艾滋病毒/艾滋病。频繁发生的影响 肌肉萎缩包括虚弱、活动障碍、跌倒、住院时间延长、康复延迟、丧失 独立生活和更高的死亡率。然而，尽管它具有广泛的临床影响，但骨骼肌 萎缩症缺乏药物治疗，因此代表着巨大的未得到满足的医疗需求。一个主要目标 Emmyon，Inc.将发现和开发一种治疗骨骼肌萎缩的药物。在我们的阶段 在SBIR项目中，我们发现了一种机密的专利小分子化合物(EMMY1- 06)，显著增加力量和肌肉质量，并显著减少制动引起的 肌肉萎缩。此外，我们还发现EMMY1-06‘S对骨骼肌的有益作用是伴随的 通过显著减少脂肪质量，从而增加对肥胖和肥胖相关血糖的保护 不宽容。在这项第二阶段的SBIR建议中，我们寻求通过推进 EMMY1-06及其相关分子作为治疗骨骼肌萎缩药物的研究进展 相关的代谢紊乱。具体来说，我们将进一步研究EMMY1-06‘S的安全性、有效性和 饮食诱导的肥胖和葡萄糖致小鼠骨骼肌萎缩模型的作用机制 这些研究将极大地推动EMMY1-06的最终发展和 在SBIR第三阶段商业化。在我们详细研究EMMY1-06的同时，我们将设计、 合成和表征结构上与EMMY1-06相关的新化合物，寻求鉴定 具有类似或甚至更好的药理特性的其他化合物 EMMY1-06。总之，这些研究将严格推动科学理解和商业 开发一种非常有前途的治疗骨骼肌萎缩的新型药物。

PROJECT SUMMARY / ABSTRACT Skeletal muscle atrophy diminishes the health and quality of life of tens of millions of people in the US alone. Frequent causes of muscle atrophy (which often co-exist in the same patient) include aging, malnutrition, muscle disuse, critical illness, certain medications, and a broad range of chronic illnesses including cancer, heart failure, COPD, diabetes, renal failure, cirrhosis, rheumatoid arthritis, and HIV/AIDS. Frequent effects of muscle atrophy include weakness, impaired activity, falls, prolonged hospitalization, delayed rehabilitation, loss of independent living, and increased mortality. However, despite its broad clinical impact, skeletal muscle atrophy lacks a pharmacologic therapy and thus represents an enormous unmet medical need. A major goal of Emmyon, Inc. is to discover and develop a pharmaceutical for skeletal muscle atrophy. In our Phase I SBIR project, we discovered and patented a confidential and proprietary small molecule compound (EMMY1- 06) that significantly increases strength and muscle mass and significantly reduces immobilization-induced muscle atrophy. In addition, we found that EMMY1-06’s beneficial effects on skeletal muscle are accompanied by striking reductions in fat mass, resulting in additional protection against obesity and obesity-related glucose intolerance. In this Phase II SBIR proposal, we seek to continue this exciting work by advancing the development of EMMY1-06 and related molecules as pharmaceuticals for skeletal muscle atrophy and related metabolic disorders. Specifically, we will further investigate EMMY1-06's safety, efficacy, and mechanisms of action in mouse models of skeletal muscle atrophy and diet-induced obesity and glucose intolerance; together, these studies will significantly advance EMMY1-06 towards final development and commercialization in SBIR Phase III. In parallel to our detailed studies of EMMY1-06, we will design, synthesize and characterize novel compounds that are structurally related to EMMY1-06, seeking to identify additional compounds with pharmacologic properties that are similar to or perhaps even better than those of EMMY1-06. Together, these studies will rigorously advance the scientific understanding and commercial development of a highly promising new class of pharmaceutical agents for skeletal muscle atrophy.