Table 1.
Summary of the biological activities of antimalarial agents from MMV400 library for inhibition of ezrin function
| Compound ID | KD (μM)a | Migration inhibitionb |
Ezrin MO-like phenotypec |
Prevention of lung metastasisd |
MMV400 library set |
Lipinski&Veber drug criteria violation counte |
|---|---|---|---|---|---|---|
| NSC305787 | 6.6 ± 3.6 (n=6) | yes | potent | yes | not applicable | 1 |
| MMV667492 | 29.4 ± 4.4 (n=2) | yes | potent | yes | probe-like | 0 |
| MMV020549 | 10.7 ± 0.4 (n=3) | no* | potent | yes | drug-like | 0 |
| MMV666069 | 2.1 ± 1.0 (n=5) | yes | moderate/subtle | yes | drug-like | 0 |
| MMV020243 | 14.8 ± 3.9 (n=6) | yes | moderate/subtle | no | probe-like | 0 |
| MMV665977 | 3.1 ± 1.6 (n=5) | yes | no | yes | probe-like | 0 |
| MMV666103 | 2.6 ± 1.0 (n=4) | yes | no | nd** | drug-like | 0 |
| MMV006172 | 6.1 ± 2.8 (n=3) | yes | no | nd | probe-like | 1 |
| MMV396680 | nd | no | moderate/subtle | nd | probe-like | 1 |
| MMV000448 | nd | nd | no | nd | probe-like | 0 |
Binding affinities of compounds for ezrin were determined by SPR. The results are expressed as mean ± standard deviations. n indicates number of separate experiments for calculation of the final KD values.
Compounds demonstrated greater inhibition of high-ezrin expressing K7M2 OS cell migration than less aggressive K12 cells.
Compounds produced ezrin MO-like phenotypes in zebrafish embryonic developmental assays.
Compounds inhibited metastatic progression of GFP-expressing osteosarcoma cells in ex vivo lung organ culture assay.
Values represent number of conditions violated over total six conditions.
According to the Lipinski’s and Veber’s druglikeness 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).
no: not observed
nd: not determined