CCT369260
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, Kd) | TR-FRET: IC50 = 520 nM (mean, n = 11); proteasome dependent monovalent BCL6 degrader. |
| Selectivity within target family: > 30-fold | Selective by proteomics vs 17 BTB/ZF domain proteins: BACH2, MYNN, ZBTB1, ZBTB5, ZBTB7A, ZBTB9, ZBTB10, ZBTB11, ZBTB17, ZBTB21, ZBTB24, ZBTB39, ZBTB40, ZBTB43, ZBTB44, ZBTB48, ZNF131No binding was observed in a BACH2 NanoBRET assay with 10 analogue compounds |
| Selectivity outside target family | PDSP panel 39 / 48 assays < 50% at 10 μM; Closest off-targets (Ki [nM]): OPRM1 (870), PBR (1100), HRH3 (2300), TMEM97 (2500), ADRB3 (4000), SLC6A3 (5100), HTR1D (6200)SGC panel: No binding at 20 μM by thermal shift (99 kinases and 3 bromodomains)IonWorks KCNH2 (hERG): IC50 = 42 μM |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | Surpasses criterion: MSD (Meso Scale Discovery) degrader assay: DC50 = 49 nM (OCI-Ly1 cells) full degrader, 62 nM (Karpas 422 cells)Immunofluorescence-based BCL6 degradation assay in SUDHL-4 cells: DC50 = 90 nM (compound conc. at which 50% of endogenous BCL6 protein is degraded), Dmax > 85 %GI50 [nM]: OCILy1 cells (35), KARPAS (27), SUDHL-4 (92), OCI-Ly3 (1610) |
| Control compound (100 times less potent than the probe) | CCT393732: TR-FRET: IC50 = 21 μM; MSD degrader assay: inactive at 10 μM |