Table 1.
IL-23R binding affinity and potency of JNJ-77242113 against IL-23–mediated responses in cells.
| In vitro protein/cells | Binding affinity/IL-23–induced endpoint | JNJ-77242113 KD or IC50 (pM) | KD/IC50 rangec | nd |
|---|---|---|---|---|
| Human IL-23R ECD (SPR in vitro) | Binding affinity (KD) | 7.1 ± 2.5 | 4–10 | 5 |
| Human PBMC | IL-23–induced STAT3 phosphorylation | 5.6 ± 1.2 | 4.3–6.6 | 3 |
| Human PBMC | IL-12–induced STAT4 phosphorylationa | > 2,000,000 | – | 2 |
| Human NK cells | IL-23–induced IFNγ production | 18.4 ± 6.2 | 12.4–28.3 | 5 |
| Human (healthy) whole blood | IL-23–induced IFNγ production | 11b | 4–91 | 15 |
| Human (psoriasis) whole blood | IL-23–induced IFNγ production | 9b | 0.5–35 | 4 |
| Rat IL-23R ECD (SPR in vitro) | Binding affinity (KD) | 17.5 ± 7.8 | 12–23 | 2 |
| Rat whole blood | IL-23–induced IL-17A production (20 ng/mL IL-23) | 250 ± 62 | 160–340 | 6 |
| Rat whole blood | IL-23–induced IL-17A production (4 ng/mL IL-23) | 54 ± 34 | 12–110 | 8 |
ECD extracellular domain, IC50 50% inhibitory concentration, IFN interferon, IL interleukin, KD disassociation constant, NK natural killer, PBMC peripheral blood mononuclear cells, SPR surface plasmon resonance, STAT signal transducer and activator of transcription.
aImpact on IL-12 signaling in same PBMCs to assess selectivity.
bValues for human whole blood IC50s are median values; all others are mean values.
cRange indicates minimum and maximum values obtained across independent experiments.
dNumber of independent experiments, n.