Ivanenkov Yan A, Chufarova Nina V
Moscow Institute of Physics & Technology (State University), 9 Institutskiy lane, Dolgoprudny city, Moscow Region, 141700, Russian Federation.
Pharm Pat Anal. 2014 Jan;3(1):65-85. doi: 10.4155/ppa.13.75.
Arginase is an enzyme that metabolizes L-arginine to L-ornithine and urea. In addition to its fundamental role in the hepatic ornithine cycle, it also influences the immune systems in humans and mice. Arginase participates in many inflammatory disorders by decreasing the synthesis of nitric oxide and inducing fibrosis and tissue regeneration. L-arginine deficiency, which is modulated by myeloid cell arginase, suppresses T-cell immune response. This mechanism plays a fundamental role in inflammation-associated immunosuppression. Pathogens can synthesize their own arginase to elude immune reaction. Small-molecule arginase inhibitors are currently described as promising therapeutics for the treatment of several diseases, including allergic asthma, inflammatory bowel disease, ulcerative colitis, cardiovascular diseases (atherosclerosis and hypertension), diseases associated with pathogens (e.g., Helicobacter pylori, Trypanosoma cruzi, Leishmania, Mycobacterium tuberculosis and Salmonella), cancer and induced or spontaneous immune disorders. This article summarizes recent patents in the area of arginase inhibitors and discusses their properties.
精氨酸酶是一种将L-精氨酸代谢为L-鸟氨酸和尿素的酶。除了在肝脏鸟氨酸循环中的基本作用外，它还影响人类和小鼠的免疫系统。精氨酸酶通过减少一氧化氮的合成以及诱导纤维化和组织再生参与多种炎症性疾病。由髓样细胞精氨酸酶调节的L-精氨酸缺乏会抑制T细胞免疫反应。这种机制在炎症相关的免疫抑制中起重要作用。病原体可以合成自身的精氨酸酶以逃避免疫反应。小分子精氨酸酶抑制剂目前被认为是治疗多种疾病的有前景的疗法，这些疾病包括过敏性哮喘、炎症性肠病、溃疡性结肠炎、心血管疾病（动脉粥样硬化和高血压）、与病原体相关的疾病（如幽门螺杆菌、克氏锥虫、利什曼原虫、结核分枝杆菌和沙门氏菌）、癌症以及诱导性或自发性免疫疾病。本文总结了精氨酸酶抑制剂领域的近期专利并讨论了它们的特性。
