Medication Class Introduction

Aminosalicylates, introduced in the 1940s, were the first class of pharmacologic agents developed for the treatment of inflammatory bowel disease (IBD).¹ Their therapeutic effects are attributed to the active compound, 5-aminosalicylic acid (5-ASA).^1,2

IBD Treatment Landscape^3–13

JAK=Janus kinase; S1P=sphingosine-1-phosphate; TNF=tumor necrosis factor.

Role in IBD Pathogenesis

IBD is characterized by increased cytokine production resulting from activation of intracellular signaling pathways.¹⁴ This may be partly attributed to decreased activity of the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ), which typically helps regulate some of these signaling pathways.^14–16 In individuals with IBD, PPARγ expression may be reduced, potentially leading to dysregulated signaling and elevated cytokine production.^14–16

DNA=deoxyribonucleic acid; PPARγ=peroxisome proliferator-activated receptor gamma.

Mechanism of Action in IBD

Following aminosalicylate administration in IBD, 5-ASA is transported from the intestinal lumen into the cytoplasm of intestinal epithelial cells.^15,16 Within the cytoplasm, 5-ASA binds to PPARγ, which then translocates to the nucleus.^15,16 There, PPARγ forms a complex with the transcription factor retinoid X receptor (RXR) that binds to DNA, initiating transcription of anti-inflammatory genes and subsequently downregulating inflammatory signaling pathways and cytokine production.^14–16

5-ASA=5-aminosalicylic acid; DNA=deoxyribonucleic acid; PPARγ=peroxisome proliferator-activated receptor gamma; RXR=retinoid X receptor.