Progress in the development of aminopeptidase N (APN/CD13) inhibitors.
Aminopeptidase N (APN; CD13) is a member of zinc-containing ectoenzymes family involved in the degradation of neutral or basic amino acids (Ala>Phe>Leu>Gly) from N-terminal of bioactive peptides and amide or arylamide derivatives of amino acids. The expression of APN being up regulated has been implicated in the pathogenesis of a variety of diseases such as cancer, leukemia, diabetic nephropathy, and rheumatoid arthritis. Thus, APN inhibitors (APNIs) are expected to be useful for the treatment of these disorders. This article reviews briefly the structure characteristic and possible function of APN. The proposed biomolecular structures and mechanism of action used in the design of APNIs are thoroughly covered. Major emphasis is on recently published potent, small molecular weight APNIs and their essential structure activity relationship (SAR). Finally, available clinical results of compounds in development are summarized in this review.
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shan Dong University, 44 West Culture Road, Ji'nan 250012, P.R.China. xuwenf@sdu.edu.cn
Wenfang
W
Xu
Qianbin
Q
Li
D000818:Animals; D018826:CD13 Antigens / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D015394:Molecular Structure; D013379:Substrate Specificity
D004791:Enzyme Inhibitors; D018826:CD13 Antigens