Ref-1 is a novel target upstream of TNFα, IL-23, JAKi, TL1A and α4β7 biology

APX3330 inhibits overexpressed Ref-1 activity; Ref-1 is elevated in IBD (UC/Crohn’s).

Ref-1’s redox function converts transcription factors (TFs) into their active form, which binds DNA and switches on gene activation. APX3330 inhibits this redox function, so the activation step is blocked.

How APX3330 acts on Ref-1 Redox function APX3330 Ref-1 Ref-1 TFs TFs Activation How APX3330 acts on Ref-1 APX3330 Redox function Ref-1 Ref-1 TFs TFs Activation

Ref-1 drives four transcription factors behind validated IBD targets

TNFα | NF-κB pathwayTNFα, IL-6, IL-8, MCP-1/CCL2 TL1A | RemodelingHIF1α, AP-1, TL1A IL-23 | Th17 pathwayIL-23, IL-17A, IL-22 α4β7 | TraffickingMAdCAM-1, chemokines JAK/STAT signalingJaki Heme inflammationpathway NF-κB AP-1 STAT3 HIF-1α

NF-κB

  • TNFα | NF-κB pathway

    TNFα, IL-6, IL-8, MCP-1/CCL2

  • TL1A | Remodeling

    HIF1α, AP-1, TL1A

  • α4β7 | Trafficking

    MAdCAM-1, chemokines

    Heme inflammation pathway

AP-1

  • TL1A | Remodeling

    HIF1α, AP-1, TL1A

STAT3

  • IL-23 | Th17 pathway

    IL-23, IL-17A, IL-22

    JAK/STAT signaling

    Jaki

HIF-1α

  • TL1A | Remodeling

    HIF1α, AP-1, TL1A

TFs = transcription factors. Select molecules in the pathway are shown, others not listed. Ref-1 = APE-1. Sources: Kelley et al. publications.

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