Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine , The University of Texas Health Science Center at Houston,The Graduate School of Biomedical Sciences at Houston , Department of Integrative Biology and Pharmacology , 1825 Pressler St. 530C, Houston, TX 77030 , USA +1 713 500 2439 ; +1 713 500 2447 ;
Expert Opin Drug Discov. 2011 Nov;6(11):1139-54. doi: 10.1517/17460441.2011.613933. Epub 2011 Aug 25.
It is becoming increasingly clear that many diseases are characterized or associated with perturbations in nitric oxide (NO) production/signaling. Therapeutics or strategies designed to restore normal NO homeostasis will likely have broad application and utility in human health. This highly complex and multi-step pathway for NO production and subsequent target activation provides many steps in the endogenous pathway that may be useful targets for drug development. Important therapeutic areas for NO-based therapies are inflammatory disorders, cardiovascular diseases, erectile dysfunction and metabolic disorders.
The following review will discuss the endogenous NO pathway, highlight the current market and indications for NO-based therapeutics, as well as identify pathway targets currently under drug development. Each step along the NO pathway will be discussed including exogenous sources of NO, use of precursors to promote NO production and downstream pathways affected by NO production with advantages and disadvantages highlighted for each.
Development of NO-based therapeutics is and will continue to be a major focus of biotech and pharmaceutical companies. Understanding and utilizing dietary and nutritional strategies to restore NO homeostasis could allow for safer, quicker marketing of products that may be just as efficacious as drugs designed against specific targets.
越来越多的证据表明,许多疾病的特征或与其一氧化氮(NO)生成/信号转导的改变有关。旨在恢复正常 NO 动态平衡的治疗方法或策略可能在人类健康中有广泛的应用和实用价值。NO 生成和随后的靶标激活的这一高度复杂和多步骤途径提供了许多内源性途径中的步骤,这些步骤可能是药物开发的有用靶点。基于 NO 的治疗的重要治疗领域包括炎症性疾病、心血管疾病、勃起功能障碍和代谢紊乱。
本综述将讨论内源性 NO 途径,重点介绍基于 NO 的治疗方法的当前市场和适应证,以及确定当前处于药物开发阶段的途径靶点。将讨论 NO 途径的每一步,包括外源性 NO 源、使用前体来促进 NO 生成以及受 NO 生成影响的下游途径,并突出每个途径的优缺点。
基于 NO 的治疗方法的开发一直是生物技术和制药公司的主要关注点。了解和利用饮食和营养策略来恢复 NO 动态平衡,可以更安全、更快地推出产品,这些产品的功效可能与针对特定靶点设计的药物一样有效。