Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, 3001 Mercer University Drive, Atlanta, GA 30341, USA.
Department of Chemistry and Physics, Santa Rosa Junior College, Santa Rosa, CA 95401, USA.
Molecules. 2022 Jan 2;27(1):273. doi: 10.3390/molecules27010273.
Under normal physiological conditions, the kynurenine pathway (KP) plays a critical role in generating cellular energy and catabolizing tryptophan. Under inflammatory conditions, however, there is an upregulation of the KP enzymes, particularly kynurenine 3-monooxygenase (KMO). KMO has garnered much attention due to its production of toxic metabolites that have been implicated in many diseases and disorders. With many of these illnesses having an inadequate or modest treatment, there exists a need to develop KMO inhibitors that reduce the production of these toxic metabolites. Though prior efforts to find an appropriate KMO inhibitor were unpromising, the development of a KMO crystal structure has provided the opportunity for a rational structure-based design in the development of inhibitors. Therefore, the purpose of this review is to describe the kynurenine pathway, the kynurenine 3-monooxygenase enzyme, and KMO inhibitors and their potential candidacy for clinical use.
在正常生理条件下，犬尿氨酸途径 (KP) 在产生细胞能量和分解色氨酸方面起着关键作用。然而，在炎症条件下，KP 酶，特别是犬尿氨酸 3-单加氧酶 (KMO) 的表达上调。由于其产生的有毒代谢物与许多疾病和障碍有关，KMO 引起了广泛关注。由于许多这些疾病的治疗效果不佳或中等，因此需要开发能够减少这些有毒代谢物产生的 KMO 抑制剂。尽管以前寻找合适的 KMO 抑制剂的努力并不成功，但 KMO 晶体结构的发展为抑制剂的合理基于结构的设计提供了机会。因此，本综述的目的是描述犬尿氨酸途径、犬尿氨酸 3-单加氧酶酶和 KMO 抑制剂及其在临床应用中的潜在候选药物。
