Table 1.
Preclinical pharmacology of spebrutinib (CC-292)
| Enzyme or cell type | Assay | Spebrutinib (IC50 or % inhibition) |
|---|---|---|
| BTK | Enzymatic activity | < 0.5 nM |
| B cell | PLCγ2 phosphorylation (anti-IgM + CpG) | < 0.1 μM |
| B cell | Proliferation (anti-IgM + CpG) | 0.7 μM |
| B cell | CD86, CD40, CD54, CD69 expression | ~ 50% @ 1 μM |
| B cell | IL-6 production | 9% @ 3 μM |
| 85% @ 10 μM | ||
| B cell | Plasmablast differentiation | 87.5% @ 10 μM |
| B cell | IgG production | 52% @ 1 μM |
| T cell | TCR stimulation proliferation | 4.6 μM |
| T cell | Interferon-γ production | 0% @ 0.1 μM |
| 93% @ 1 μM | ||
| 99% @ 10 μM | ||
| T cell | Degranulation | 83% @ 10 μM |
| NK cells | Degranulation | 92% @ 10 μM |
| Macrophage | FcγR-induced TNF-α production | 42% @ 1 μM |
| Myeloid dendritic cells | TLR9-induced CD86 expression | 94% @ 0.1 μM |
| Basophils | FcεR-induced degranulation | < 1 μM |
| Osteoclasts | Osteoclastogenesis | 66% @ 0.1 μM |
BTK Bruton’s tyrosine kinase, FcεR Fc-epsilon receptor, FcγR Fc-gamma receptor, IL interleukin, PLCγ2 phospholipase Cγ2, TCR T-cell receptor, TLR9 Toll-like receptor 9, TNF-α tumor necrosis factor-α