Table 4.

Plk1 PBD domain inhibitors

Compound (chemical class)	Structure	Mode of action	IC50/Selectivity	References
PRECLINICAL
Thymoquinone		Inhibits PBD-dependent binding & subcellular localization	Plk1 IC50 = 1.14 ± 0.04 μM Plk2 IC50 = 1.9 ± 0.1 μM Plk3 IC50 = 22.4 ± 0.8 μM	[109]
Poloxin (thymoquinone derivative)		Inhibits in vitro PBD-dependent binding & subcellular localization	Plk1 IC50 = 4.8 ± 1.3 μM Plk2 IC50 = 18.7 ± 1.8 μM Plk3 IC50 = 53.9 ± 8.5 μM	[110]
Poloxipan		Pan inhibitor of Plk1–3 PBDs	Plk1 IC50 = 3.2 ± 0.3 μM Plk2 IC50 = 1.7 ±0.2 μM Plk3 IC50 = 3.0 ± 0.1 μM	[110]
Purpurogallin (benzotropolone-containing compound)		Inhibits PBD-dependent binding in vitro and in vivo	Plk1 IC50 < 0.3 μM inhibits PBD of PLK2 but not of PLK3	[111]
4j derivatives		Inhibits PBD-dependent binding in vitro	Plk1 IC50 4j = 3 nM (320 μM)† 4j* = 3 nM (85 μM)† 3c = 1 nM (85 μM)† 4c = 2 nM (55 μM)	[106,112]

ND, Not determined; EC₅₀, effector concentration for half-maximum response; IC₅₀, half-maximal inhibitory concentration; PBD, polo box domain; PLK, polo-like kinase.

^†Extracellular concentration required to achieve 50% mitotic block in cultured HeLa cells.