Table 2. Chemical analogs of M0.
We designed and synthesized a series of 27 M0 derivatives, and tested each of these for inhibition of human Mcl-1 using a fluorescence polarization competition assay (see Supplementary Methods). This series of analogs was designed without consideration of DARC’s model of the M0/Mcl-1 complex, to allow unbiased evaluation of the model.
| Compound | Chemical structure | Ki (µM) | L.E. (kcal/mol•heavyatom) |
|---|---|---|---|
| M0 |  |
21 | 0.27 |
| D1 |  |
2 | 0.29 |
| D2 |  |
3 | 0.30 |
| D3 |  |
7 | 0.33 |
| D4 |  |
10 | 0.31 |
| D5 |  |
28 | 0.33 |
| D6 |  |
20 | 0.32 |
| D7 |  |
40 | 0.25 |
| D8 |  |
>50 | N.D. |
| D9 |  |
>50 | N.D. |
| D10 |  |
>50 | N.D. |
| D11 |  |
>50 | N.D. |
| D12 |  |
>50 | N.D. |
| D13 |  |
>50 | N.D. |
| D14 |  |
>50 | N.D. |
| D15 |  |
>50 | N.D. |
| D16 |  |
>50 | N.D. |
| D17 |  |
>50 | N.D. |
| D18 |  |
>50 | N.D. |
| D19 |  |
>50 | N.D. |
| D20 |  |
>50 | N.D. |
| D21 |  |
>50 | N.D. |
| D22 |  |
>50 | N.D. |
| D23 |  |
>50 | N.D. |
| D24 |  |
>50 | N.D. |
| D25 |  |
>50 | N.D. |
| D26 |  |
>50 | N.D. |
| D27 |  |
>50 | N.D. |