Table 2.
Characterization of pharmacological inhibitors in phenotypic assays.
| Chemical | Target | PBMC | Primary B cell | Namalwa | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| MLR | IgG production | Viability WST-1 | CD40 | CD69 | CD70 | CD80 | CD83 | CD86 | ||
| Bortezomib | Proteasome: 30–100 | 35 | 90 | 10 | — | — | — | — | — | — |
| Ibrutinib | BTK: 0.5 | 4 000 | <1 | 1 800 | 690 | ↗ | 670 | >3 000 | 730 | <30 |
| Chloroquine | TLR 3, 7, 8, and 9: 560 | >10 000 | 95 | >10 000 | 70 | 90 | 1 000 | 60 | 210 | <30 |
| Dasatinib | SRC: 0.55 BCR/ABL: 3 LYN: 8.5 Other TK |
15 | 55 | 20 | — | — | — | — | — | — |
| LY-294,002 hydrochloride | PI3K: 3 000 | 5 100 | 670 | 4 600 | 2 800 | >3 000 | 2 500 | 2 200 | >3 000 | 450 |
| MK-2206 2HCl | AKT1/2/3: 8/12/65 | 3 500 | 25 | 2 700 | 1 500 | ↗ | 1 200 | 1 100 | 120 | <30 |
| AZD-5363 | AKT1/2/3: 3/7/7 | 2 600 | 600 | 3 000 | 1 500 | ↗ | 850 | >3 000 | 2 200 | <30 |
| TPCA-1 | IKK-2: 17.9 IKK-1: 400 |
360 | 450 | 2 800 | 210 | 550 | 480 | 700 | 550 | <30 |
| STAT3 inhibitor VII | STAT3: 170 | 8 500 | >10 000 | >10 000 | >3 000 | >3 000 | >3 000 | 2 800 | >3 000 | 1 000 |
| SAHA | Class I & II histone deacetylase (HDAC): <86 HDAC1: 13.7 |
5 000 | 440 | 2 100 | >3 000 | ↗ | >3 000 | 1 300 | >3 000 | >3 000 |
| Mirin | Mre11-Rad50-Nbs1 (MRN) complex (DNA-repair) Cell-free: 12 000 Human: 66 000 |
>10 000 | 1 400 | >3 000 | >3 000 | >3 000 | >3 000 | >3 000 | >3 000 | >3 000 |
The table shows the IC50 (nM) of the inhibitors on the molecular target and in the different phenotypic assays: MLR with human PBMCs, IgG production by human B cell stimulated by ODN2006, and surface markers expression on ODN2006-stimulated Namalwa. Cytotoxic counterscreen (WST-1) was performed on Namalwa cells. ↗: indicates an increase in expression.