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. Author manuscript; available in PMC: 2020 Dec 15.
Published in final edited form as: Bioorg Med Chem Lett. 2019 Oct 31;29(24):126757. doi: 10.1016/j.bmcl.2019.126757

Table 1.

Summary of bioassay data for the novel benzimidazole phosphonates

Compound GGTase II
(IC50)
(μM)		 GGTase I
(IC50)
(μM)		 FTase
(IC50)
(μM)		 FDPS
(IC50) (μM)		 GGDPS
(IC50)
(μM)		 Selectivity
for FDPS
relative to
GGDPS		 Cellular
LEC1
13 198 ± 86 > 1000 125 ± 49 >100 > 100 -- 1 mM
14 810 ± 214 > 1000 > 1000 >100 > 100 -- 5 mM
15 >1000 145 ± 32 450 ± 70 >100 > 100 -- NA at ≤ 5 mM
16 >1000 > 1000 > 1000 >100 > 100 -- NA at ≤ 5 mM
17 >1000 > 1000 830 ± 50 0.024 ± 0.007 20.5 ± 4.3 854 25 μM
18 >1000 > 1000 > 1000 1.00 ± 0.11 > 100 >100 NA at ≤ 1 mM
19 738 ± 112 122 ± 13 340 ± 40 0.15 ± 0.015 87 ± 22 580 0.5 mM
20 534 ± 133 > 1000* > 1000 0.69 ± 0.29 41 ± 29 59 NA at ≤ 1 mM
1

Cellular LEC (lowest effective concentration) for FDPS inhibitors is defined as the lowest concentration for which an unmodified Rap1a band is visible in the immunoblot and a statistically significant increase in intracellular lambda light chain is observed in the ELISA. Cellular LEC for GGTase II inhibitors is defined as the lowest concentration for which there is a statistically significant increase in intracellular lambda light chains and a ≥20% decrease in Rab6 levels in the detergent fraction as assessed by immunoblot analysis.

*

A concentration-dependent increase in GGTase I activity was observed with enzyme activity of 560% relative to control at 1000 μM.

Abbreviation: NA, no activity