Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.14/176278
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- Title
- Novel indoleamine 2,3-dioxygenase-1 inhibitors from a multistep in silico screen
- Related
- Bioorganic and medicinal chemistry, Vol. 20, No. 3, (2012), p.1354-1363
- DOI
- 10.1016/j.bmc.2011.10.068
- Publisher
- Elsevier
- Date
- 2012
- Author/Creator
- Smith, Jason R
- Author/Creator
- Evans, Krystal J
- Author/Creator
- Wright, Adam
- Author/Creator
- Willows, Robert D
- Author/Creator
- Jamie, Joanne F
- Author/Creator
- Griffith, Renate
- Description
- Indoleamine 2,3-dioxygenase-1 (IDO-1) is a heme containing enzyme that catalyses the initial step in the major pathway of l-tryptophan catabolism; the kynurenine pathway. A large body of evidence has been accumulating for its immunosuppressive and tumoural escape roles and its applicability as a therapeutic target. Of particular interest is the possibility that IDO-1 inhibition may arrest, and sometimes revert, tumour growth. There exists a continuing need for the development of new and specific inhibitors for IDO-1, and we have created three pharmacophores designed to aid in this search. Initial database hits were further screened using Kier flexibility and a ‘What-If’ docking technique, designed to overcome the inherent limitations of today’s forcefields with regards to heme chemistry. Eighteen compounds were tested in vitro, yielding four novel inhibitors with low micromolar IC₅₀ values, comparable with current inhibitors.
- Description
- 10 page(s)
- Subject Keyword
- Computer-aided drug design
- Subject Keyword
- Docking
- Subject Keyword
- Heme
- Subject Keyword
- IDO inhibitors
- Subject Keyword
- Pharmacophore
- Resource Type
- journal article
- Organisation
- Macquarie University. Dept. of Chemistry and Biomolecular Sciences
- Identifier
- http://hdl.handle.net/1959.14/176278
- Identifier
- ISSN:0968-0896
- Identifier
- mq_res-ext-2-s2.0-84856224864
- Language
- eng
- Reviewed
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