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J Med Chem. 2009 Dec 10;52(23):7364-7. doi: 10.1021/jm900518f.

Discovery of potent competitive inhibitors of indoleamine 2,3-dioxygenase with in vivo pharmacodynamic activity and efficacy in a mouse melanoma model.

Author information

1
Incyte Corporation, Experimental Station, Route 141 and Henry Clay Road, Wilmington, Delaware 19880, USA.

Abstract

A hydroxyamidine chemotype has been discovered as a key pharmacophore in novel inhibitors of indoleamine 2,3-dioxygenase (IDO). Optimization led to the identification of 5l, which is a potent (HeLa IC(50) = 19 nM) competitive inhibitor of IDO. Testing of 5l in mice demonstrated pharmacodynamic inhibition of IDO, as measured by decreased kynurenine levels (>50%) in plasma and dose dependent efficacy in mice bearing GM-CSF-secreting B16 melanoma tumors.

PMID:
19507862
DOI:
10.1021/jm900518f
[Indexed for MEDLINE]

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