Indoleamine 2,3-dioxygenase (IDO) is involved in tumor immune escape and resistance to chemotherapy, and is clinically correlated with tumor progression. IDO inhibitors show marginal efficacy as single agents; therefore, combinations of these inhibitors with other therapies hold promise for cancer therapy. The aim of this study was to investigate the synergistic antitumor effects of IDO inhibit...

Natural product (NP)-inspired design principles provide invaluable guidance for bioactive compound discovery. Pseudo-natural products (PNPs) are de-novo combinations of NP fragments to target biologically relevant chemical space not covered by NPs. We describe the and synthesis apoxidoles, a novel pseudo-NP class, whereby indole- tetrahydropyridine linked in monopodal connectivity found nature....

The aim of this review is to present current information on transplantation research regarding the role of indoleamine 2,3 dioxygenase in immune regulation. We present the basic mechanisms by which the enzyme is expressed, followed by tryptophan catabolism that leads to midg1 phase arrest and apoptosis. Other effects proposed, although not yet completely proven and generally accepted, include T...

Inhibitors of fatty acid cyclooxygenase such as indomethacin (0.1 mM), phenylbutazone (0.3 mM), and aspirin (1 mM) were found to suppress almost completely the interferon-mediated induction of indoleamine 2,3-dioxygenase in mouse lung slices. However, phenacetin, an anti-inflammatory agent devoid of cyclooxygenase inhibitory activity, and sodium salicylate, a weak inhibitor of cyclooxygenase, w...

Human indoleamine 2,3-dioxygenase (hIDO), a monomeric heme enzyme, catalyzes the oxidative degradation of L-Trp and other indoleamine derivatives. Using Fourier transform infrared and optical absorption spectroscopy, we have investigated the interplay between ferrous hIDO, the ligand analog CO, and the physiological substrate L-Trp. These data provide the long sought evidence for two distinct L...

The tryptophan (TRP) to kynurenine (KYN) metabolic pathway is now firmly established as a key regulator of innate and adaptive immunity. A plethora of preclinical models suggests that this immune tolerance pathway - driven by the key and rate-limiting enzymes indoleamine-2,3-dioxygenase and TRP-2,3-dioxygenase - is active in cancer immunity, autoimmunity, infection, transplant rejection, and al...

Interferons have been shown to be potential anti-cancer agents and to inhibit tumor cell growth in culture. The in vivo mechanism of the anti-proliferative effect may be direct or indirect through the immune system; however, in vitro a primary mechanism of cytotoxicity is through the depletion of tryptophan. In particular, interferon-7 (IFN-y) induces an enzyme of tryptophan catabolism, indolea...

word count: 200 Blood First Edition Paper, prepublished online December 7, 2006; DOI 10.1182/blood-2006-07-034785 Copyright © 2006 American Society of Hematology only. For personal use at PENN STATE UNIVERSITY on February 23, 2013. bloodjournal.hematologylibrary.org From