Table 1 IL-23R binding affinity and potency of JNJ-77242113 against IL-23–mediated responses in cells.

From: JNJ-77242113, a highly potent, selective peptide targeting the IL-23 receptor, provides robust IL-23 pathway inhibition upon oral dosing in rats and humans

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

  1. 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.
  2. aImpact on IL-12 signaling in same PBMCs to assess selectivity.
  3. bValues for human whole blood IC50s are median values; all others are mean values.
  4. cRange indicates minimum and maximum values obtained across independent experiments.
  5. dNumber of independent experiments, n.
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