Close
Help




JOURNAL

International Journal of Tryptophan Research

137,949 Journal Article Views | Journal Analytics

The Tumor-Selective Cytotoxic Agent ß-Lapachone is a Potent Inhibitor of IDO1

Submit a Paper



Publication Date: 19 Aug 2013

Type: Original Research

Journal: International Journal of Tryptophan Research

Citation: International Journal of Tryptophan Research 2013:6 35-45

doi: 10.4137/IJTR.S12094

Abstract

β-lapachone is a naturally occurring 1,2-naphthoquinone-based compound that has been advanced into clinical trials based on its tumor-selective cytotoxic properties. Previously, we focused on the related 1,4-naphthoquinone pharmacophore as a basic core structure for developing a series of potent indoleamine 2,3-dioxygenase 1 (IDO1) enzyme inhibitors. In this study, we identified IDO1 inhibitory activity as a previously unrecognized attribute of the clinical candidate β-lapachone. Enzyme kinetics-based analysis of β-lapachone indicated an uncompetitive mode of inhibition, while computational modeling predicted binding within the IDO1 active site consistent with other naphthoquinone derivatives. Inhibition of IDO1 has previously been shown to breach the pathogenic tolerization that constrains the immune system from being able to mount an effective anti-tumor response. Thus, the finding that β-lapachone has IDO1 inhibitory activity adds a new dimension to its potential utility as an anti-cancer agent distinct from its cytotoxic properties, and suggests that a synergistic benefit can be achieved from its combined cytotoxic and immunologic effects.


Downloads

PDF  (876.46 KB PDF FORMAT)

RIS citation   (ENDNOTE, REFERENCE MANAGER, PROCITE, REFWORKS)

BibTex citation   (BIBDESK, LATEX)

XML






What Your Colleagues Say About International Journal of Tryptophan Research
Publishing in the International Journal of Tryptophan Research was a smooth and efficient process. I was kept extremely well informed of the progress of my publication and the review process was thorough, positive and formative. I look forward to repeating the experience in the near future.
Dr Simon P. Jones (St Vincent’s Center for Applied Medical Research, University of New South Wales, Sydney, Australia)
More Testimonials

Quick Links


New article and journal news notification services