Table 4. Overview of Key Compoundsa.
| BCL6 TR-FRET IC50 (nM)b | MSD degrader assay [OCI-Ly1] DC50 (nM) [Dmax]b | Calculated free DC50 [OCI-Ly1] (nM) | fu,media | CLint (HLM/MLM/RLM) μL/min/mg protein | log D7.4c | aq. sol. (μM)d | PAMPA (pH 7.4)/×10–6 cm s–1 | |
|---|---|---|---|---|---|---|---|---|
| 2 CCT369260 | 523 | 54 [99%] | 1.2 | 0.022 | 11/78/10 | 4.3 | 11 | 33 |
| 5 | 95 | 35 [89%] | 12.4 | 0.37 | 28/122/14 | 2.3 | 40 | 23 |
| 9a | 1.5 | 2.7 [83%] | 0.24 | 0.088 | 14/142/9 | 3.2 | 13e | 21 |
| 12a CCT373566 | 2.2 | 0.7 [92%] | 0.088 | 0.13 | 8/116/3 | 3.0 | 10 | 24 |
| 12b CCT373567 | 2.9 | >2000 [>30%] | NT | NT | 3/90/3 | 2.9 | 8 | 16 |
a
NT = not tested.
b
Data represent the geometric mean of at least three replicates. See Supporting Information Tables S1 and S2 for full statistics.
c
Measured log D determined using the Chrom log D method.
d
Kinetic solubility measured by NMR in HEPES buffer at pH 8, containing 4% DMSO.
e
Indicates solubility measured by HPLC in PBS buffer and 1% DMSO at pH 7.4.