CLL cell apoptosis induced by nitric oxide synthase inhibitors: correlation with lipid solubility and NOS1 dissociation constant.
Publication/Presentation Date
7-1-2008
Abstract
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.
Volume
32
Issue
7
First Page
1061
Last Page
1070
ISSN
0145-2126
Published In/Presented At
Levesque, M. C., Ghosh, D. K., Beasley, B. E., Chen, Y., Volkheimer, A. D., O'Loughlin, C. W., Gockerman, J. P., Moore, J. O., & Weinberg, J. B. (2008). CLL cell apoptosis induced by nitric oxide synthase inhibitors: correlation with lipid solubility and NOS1 dissociation constant. Leukemia research, 32(7), 1061–1070. https://doi.org/10.1016/j.leukres.2007.11.026
Disciplines
Medicine and Health Sciences
PubMedID
18180035
Department(s)
Fellows and Residents
Document Type
Article