Phenotypic assay data for probe BAY-7598
Primary screening
B cells play a central role in the pathology of systemic autoimmune diseases such as Systemic Lupus Erythematosus (SLE) and myositis through the secretion of autoantibodies. Autoantibodies can form immune complexes, which can drive inflammation in part through interferon type I induction. In this assay the probe was tested for the inhibition of IgG and IgM secretion in peripheral blood mononuclear cells. Read more
Probe concentration: 0.001 uM
Results
All data are normalised to vehicle control (DMSO at < 0.1 %). The criteria for the conclusion are:
- A paired t-test with p < 0,05 compared to vehicle control
- An average > 50% reduction of IgG and IgM, while 15-50% reduction means a slight effect.
Conclusion: BAY-7598 does not show any inhibitory effect.
| Healthy controls | Systemic Lupus Erythematosus patients | Myositis patients | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| HC1 | HC2 | HC3 | HC4 | HC5 | HC6 | HC7 | HC8 | SLE1 | SLE2 | SLE3 | M1 | M2 | M3 | M4 | M5 | Method | |
| IgG | 0.61 | 0.93 | 0.64 | 1.03 | 0.86 | 0.96 | 2.33 | 1.89 | 16.38 | 1.01 | 1.22 | 0.93 | ELISA | ||||
| IgM | 0.94 | 1.02 | 1.94 | 1.27 | 2.64 | 1.12 | 2.36 | 0.34 | 1.01 | 1.44 | 0.21 | 2.03 | ELISA | ||||
| Viability | 0.87 | 1.04 | 1.28 | 1.29 | 1.02 | 1.31 | 1.05 | 1.18 | 1.29 | 0.91 | 1.20 | 1.13 | CellTiter-Glo | ||||
Cytokines such as IL-1β, IL-6, IL-8 and TNF (tumor necrosis factor) play a role in inflammatory bowel disease, including ulcerative colitis (UC) and Crohn's disease (CD). In this assay the probe was added to whole blood from healthy donors and patients and the muramyl dipeptide (MDP)-induced cytokine response was measured. Read more
Probe concentration: 0.001 uM
Results
All data are normalised to vehicle control (DMSO at < 0.1 %). Prednisolone was used as positive control. Prednisolone results are included in the downloadable data file. The criteria for the conclusion are:
- A paired t-test with p < 0,05 compared to vehicle control
- An average > 50% reduction of the tested cytokine.
Conclusion: BAY-7598 does not reduce MDP-induced cytokine secretion significantly.
| Ulcerative colitis patients | Crohn's disease patients | Healthy controls | ||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cytokine | UC1 | UC2 | UC3 | UC4 | UC5 | UC6 | CD1 | CD2 | CD3 | CD4 | CD5 | CD6 | CD7 | CD8 | CD9 | CD10 | HC1 | HC2 | HC3 | HC4 | HC5 | HC6 | Average | t-test |
| IL-1beta | 1.33 | 0.51 | 2.92 | 0.73 | 1.00 | 0.41 | 1.47 | 0.73 | 0.80 | 0.96 | 0.62 | 1.06 | 1.00 | 0.53 | 0.63 | 0.83 | 0.64 | 0.94 | 1.34 | 1.58 | 0.61 | 0.98 | Not significant | |
| IL-6 | 0.86 | 0.87 | 2.24 | 0.74 | 0.95 | 0.73 | 0.85 | 1.21 | 0.73 | 1.41 | 0.83 | 0.92 | 1.15 | 0.93 | 0.80 | 1.00 | 0.93 | 1.19 | 1.24 | 1.18 | 1.22 | 0.68 | 1.03 | Not significant |
| IL-8 | 0.96 | 0.76 | 1.94 | 0.81 | 0.80 | 0.70 | 1.19 | 0.72 | 1.21 | 0.97 | 0.98 | 1.50 | 1.89 | 0.54 | 0.55 | 0.82 | 0.97 | 0.78 | 1.37 | 0.80 | 1.33 | 0.75 | 1.02 | Not significant |
| TNF | 1.92 | 0.36 | 1.23 | 0.52 | 1.31 | 0.58 | 1.30 | 2.18 | 0.89 | 2.50 | 0.84 | 2.02 | 1.24 | 2.09 | 1.96 | 1.06 | 1.06 | 1.08 | 0.70 | 0.83 | 0.63 | 1.25 | Not significant | |