Macchiarulo Antonio, Camaioni Emidio, Nuti Roberto, Pellicciari Roberto
Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia, via del Liceo 1, 06123 Perugia, Italy.
Amino Acids. 2009 Jul;37(2):219-29. doi: 10.1007/s00726-008-0137-3. Epub 2008 Jul 9.
Indoleamine 2,3-dioxygenase (IDO) catalyzes the first and rate-limiting step of Kynurenine pathway along the major route of Tryptophan catabolism. The scientific interest in the enzyme has been growing since the observations of the involvement of IDO in the mechanisms of immune tolerance and in the mechanisms of tumor immuno-editing process. In view of this latter observation, in particular, preclinical studies of small molecule inhibitors of the enzyme have indicated the feasibility to thwart the immuno-editing process and to enhance the efficacy of current chemotherapeutic agents, supporting the notion that IDO is a novel target in cancer disease.This review covers the structural and conformational aspects of substrate recognition by IDO, including the catalytic mechanism and the so-far puzzling mechanisms of enzyme activation. Furthermore, we discuss the recent advances of medicinal chemistry in the field of IDO inhibitors.
吲哚胺2,3-双加氧酶（IDO）催化色氨酸分解代谢主要途径中犬尿氨酸途径的第一步及限速步骤。自从观察到IDO参与免疫耐受机制和肿瘤免疫编辑过程机制以来，对该酶的科学兴趣一直在增长。特别是鉴于后一种观察结果，该酶小分子抑制剂的临床前研究表明，挫败免疫编辑过程并提高当前化疗药物疗效是可行的，这支持了IDO是癌症疾病新靶点的观点。本综述涵盖了IDO底物识别的结构和构象方面，包括催化机制以及迄今为止令人困惑的酶激活机制。此外，我们还讨论了IDO抑制剂领域药物化学的最新进展。
