@article{9d625956a06146859b16ede3c650dcf2,
title = "In vitro studies in a myelogenous leukemia cell line suggest an organized binding of geranylgeranyl diphosphate synthase inhibitors",
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 1 μM 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.",
author = "Reilly, {Jacqueline E.} and Xiang Zhou and Huaxiang Tong and Kuder, {Craig H.} and Wiemer, {David F.} and Hohl, {Raymond J.}",
note = "Funding Information: Financial support from the NIH Predoctoral Training Program in the Pharmacological Sciences ( 2 T32 GM067795 , to JER), the Roy J. Carver Charitable Trust as a Research Program of Excellence, and the Roland W. Holden Family Program for Experimental Cancer Therapeutics is gratefully acknowledged. Funding sources were not involved in the conduct of the research; preparation of the article; study design; collection, analysis, and interpretation of the data; writing of the report; or decision to submit the article for publication. RJH and DFW are co-founders of Terpenoid Therapeutics Incorporated and hold an equity interest in this company. RJH and DFW are named inventors on patents held by the UI that describe the preparation and use of bisphosphonates including DGBP (3), and additional compounds tested here. Publisher Copyright: {\textcopyright}2015 Published by Elsevier Inc.",
year = "2015",
month = jun,
day = "11",
doi = "10.1016/j.bcp.2015.04.009",
language = "English (US)",
volume = "96",
pages = "83--92",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier Inc.",
number = "2",
}