CLL cell apoptosis induced by nitric oxide synthase inhibitors: correlation with lipid solubility and NOS1 dissociation constant.

Journal Article

Nitric oxide synthase (NOS) inhibitors induce chronic lymphocytic leukemia (CLL) cell apoptosis and have potential as CLL therapeutics. We determined the half-maximal concentration (ED(50)) of 22 NOS inhibitors that induced CLL cell death in vitro. There was a direct correlation of the NOS1 (but not NOS2) dissociation constant (K(d)) and the hydrophobicity partitioning coefficient of each NOS inhibitor and its ED(50). NOS inhibitors that bound tightly to CLL cell NOS1 and were hydrophobic potently induced CLL cell death. CLL cell RNA and protein analyses confirmed CLL cell NOS1 expression. Our studies permit the rational selection of NOS inhibitors for testing as CLL therapeutics.

Full Text

Duke Authors

Cited Authors

  • Levesque, MC; Ghosh, DK; Beasley, BE; Chen, Y; Volkheimer, AD; O'Loughlin, CW; Gockerman, JP; Moore, JO; Weinberg, JB

Published Date

  • July 2008

Published In

Volume / Issue

  • 32 / 7

Start / End Page

  • 1061 - 1070

PubMed ID

  • 18180035

International Standard Serial Number (ISSN)

  • 0145-2126

Digital Object Identifier (DOI)

  • 10.1016/j.leukres.2007.11.026

Language

  • eng

Conference Location

  • England