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Non‐Bisphosphonate Inhibitors of Isoprenoid Biosynthesis Identified via Computer‐Aided Drug Design
Author(s) -
Durrant Jacob D.,
Cao Rong,
Gorfe Alemayehu A.,
Zhu Wei,
Li Jikun,
Sankovsky Anna,
Oldfield Eric,
McCammon J. Andrew
Publication year - 2011
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2011.01164.x
Subject(s) - farnesyl diphosphate synthase , atp synthase , bisphosphonate , chemistry , virtual screening , biochemistry , enzyme , terpenoid , drug discovery , drug , pharmacology , biology , osteoporosis , endocrinology
The relaxed complex scheme, a virtual‐screening methodology that accounts for protein receptor flexibility, was used to identify a low‐micromolar, non‐bisphosphonate inhibitor of farnesyl diphosphate synthase. Serendipitously, we also found that several predicted farnesyl diphosphate synthase inhibitors were low‐micromolar inhibitors of undecaprenyl diphosphate synthase. These results are of interest because farnesyl diphosphate synthase inhibitors are being pursued as both anti‐infective and anticancer agents, and undecaprenyl diphosphate synthase inhibitors are antibacterial drug leads.