Table 1.

Small Molecule Plk1 Inhibitor Structures, Mechanisms of Action, and Preclinical Activities

Agent/Structure	Mechanism of Action	IC50
Rigosertib (ON 01910.Na) (benzylstyryl sulphone)	Affects microtubule dynamics	Plk1 = 9-10 nM 10- to 20-fold higher concentrations were required for inhibition of Plk2 [56]
Volasertib (BI 6727) (dihydropteridinone derivative)	ATP-competitive inhibitor	Plk1 = 0.87 nM Plk2 = 5 nM Plk3 = 56 nM [57]
GSK 461364 (thiophene derivative)	ATP-competitive inhibitor	Plk1 ≤ 0.5 nM⁎ Plk2 = 860 nM⁎ Plk3 = 1000 nM⁎[58]
GW843682 (benzimidazole thiophene)	ATP-competitive inhibitor	Plk1 = 2.2 nM Plk2 = N/A Plk3 = 9.1 nM [59]
PLHS-Pmab ((2S,3R)-2-amino-3-methyl-4-phosphonobutyric acid)	Interferes with Plk1 PBD functions in vitro and in vivo	Not reported [60]
PPG (benzotropolone-containing compound)	Inhibits PBD-dependent binding in vitro and in vivo	Plk1 = ~ 0.3 μM (in glutathione S-transferase pull-down assay) Plk2 = N/A Plk3 = N/A [61]
Poloxin (thymoquinone derivative)	Interferes with Plk1 PBD functions in vitro and in vivo	Plk1 = 4.8 μM Plk2 = 18.7 μM Plk3 = 53.9 μM [62]

N/A, not applicable.

^⁎IC₅₀ values for GSK461364A were determined on the basis of the intrinsic binding constant (K_i^⁎app), which was calculated by applying the Cheng-Prusoff relationship for a competitive inhibitor (ATP K_m^app = 16 μM) to the IC₅₀ value obtained following a 60-minute preincubation in the presence of GSK461364A [58].