Table 1.

Summary of the biologic activities of antimalarial agents from the MMV400 library for inhibition of ezrin function

Compound IDKD (μmol/L)aMigration inhibitionbEzrin MO-like phenotypecPrevention of lung metastasisdMMV400 library setLipinski and Veber drug criteria violation counte
NSC3057876.6 ± 3.6 (n = 6)YesPotentYesNot applicable1
MMV66749229.4 ± 4.4 (n = 2)YesPotentYesProbe-like0
MMV02054910.7 ± 0.4 (n = 3)noPotentYesDrug-like0
MMV6660692.1 ± 1.0 (n = 5)YesModerate/subtleYesDrug-like0
MMV02024314.8 ± 3.9 (n = 6)YesModerate/subtlenoProbe-like0
MMV6659773.1 ± 1.6 (n = 5)YesnoYesProbe-like0
MMV6661032.6 ± 1.0 (n = 4)YesnondDrug-like0
MMV0061726.1 ± 2.8 (n = 3)YesnondProbe-like1
MMV396680ndnoModerate/subtlendProbe-like1
MMV000448ndndnondProbe-like0

NOTES: According to the Lipinski and Veber drug-likeness criteria, a compound should have a low molecular weight (≤500 daltons), low partition coefficient (cLogP ≤5), low number of H-bond donor (≤5), and acceptors (≤10), low number of rotatable bonds (≤10) and low polar surface area (≤140).

Abbreviations: no, not observed; nd, not determined.

  • aBinding affinities of compounds for ezrin were determined by SPR. The results are expressed as mean ± SD. n indicates number of separate experiments for calculation of the final KD values.

  • bCompounds demonstrated greater inhibition of high-ezrin expressing K7M2 OS cell migration than less aggressive K12 cells.

  • cCompounds produced ezrin MO-like phenotypes in zebrafish embryonic developmental assays.

  • dCompounds inhibited metastatic progression of GFP-expressing osteosarcoma cells in ex vivo lung organ culture assay.

  • eValues represent number of conditions violated over total six conditions.