Journal article
In vitro studies in a myelogenous leukemia cell line suggest an organized binding of geranylgeranyl diphosphate synthase inhibitors
Biochemical pharmacology, Vol.96(2), pp.83-92
07/15/2015
DOI: 10.1016/j.bcp.2015.04.009
PMCID: PMC4831703
PMID: 25952057
Abstract
A small set of isoprenoid bisphosphonates ethers has been tested in the K562 chronic myelogenous leukemia cell line to determine their impact on isoprenoid biosynthesis. Five of these compounds inhibit geranylgeranyl diphosphate synthase (GGDPS) with IC50 values below 1μM in enzyme assays, but in cells their apparent activity is more varied. In particular, the isomeric C-geranyl-O-prenyl and C-prenyl-O-geranyl bisphosphonates are quite different in their activity with the former consistently demonstrating greater impairment of geranylgeranylation in cells but the latter showing greater impact in the enzyme assays with GGDPS. Together, these findings suggest an organized binding of these inhibitors in the two hydrophobic channels of the geranylgeranyl diphosphate synthase enzyme.
Details
- Title: Subtitle
- In vitro studies in a myelogenous leukemia cell line suggest an organized binding of geranylgeranyl diphosphate synthase inhibitors
- Creators
- Jacqueline E Reilly - Department of Pharmacology, University of Iowa, 375 Newton Rd, 5219 MERF, Iowa City, IA 52242, USAXiang Zhou - Department of Chemistry, E531 Chemistry Building, University of Iowa, Iowa City, IA 52242, USAHuaxiang Tong - Department of Internal Medicine, University of Iowa, 375 Newton Rd, 5219 MERF, Iowa City, IA 52242, USACraig H Kuder - Department of Internal Medicine, University of Iowa, 375 Newton Rd, 5219 MERF, Iowa City, IA 52242, USADavid F Wiemer - Department of Chemistry, E531 Chemistry Building, University of Iowa, Iowa City, IA 52242, USARaymond J Hohl - Department of Pharmacology, University of Iowa, 375 Newton Rd, 5219 MERF, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Biochemical pharmacology, Vol.96(2), pp.83-92
- DOI
- 10.1016/j.bcp.2015.04.009
- PMID
- 25952057
- PMCID
- PMC4831703
- NLM abbreviation
- Biochem Pharmacol
- ISSN
- 0006-2952
- eISSN
- 1873-2968
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100000002, name: NIH, award: 2 T32 GM067795; DOI: 10.13039/100001024, name: Roy J. Carver Charitable Trust; name: Roland W. Holden Family Program for Experimental Cancer Therapeutics
- Language
- English
- Date published
- 07/15/2015
- Academic Unit
- Neuroscience and Pharmacology; Chemistry; Internal Medicine
- Record Identifier
- 9983985825202771
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