IBD Drug MOAs

5-ASAs

Sulfasalazine, mesalamine, olasalazine, balsalazide

• Activates PPAR gamma cells (nuclear receptors) in colon

• Blocks COX and prostaglandins in the colon

Corticosteroids (budesonide, methylprednisolone, hydrocortisone)

• Binds to glucocorticoid receptors inside intestinal cells

Anti-TNFs

Adalimumab, golimumab, infliximab, certolizumab pegol

• Bind and attach to circulating TNF, which prevents it from binding to TNF receptor 

Ustekinumab

JAK/STAT inhibitor:

• Attaches to p40 subunit of IL-23, which prevents p19 subunit from binding to corresponding IL-12/23 receptor

Tofacitinib

JAK/STAT inhibitor:

• Inhibits phosphorylation of STAT

Upadacitinib

JAK/STAT inhibitor

• Selectively blocks JAK enzymes (primarily JAK1)

IL-23 antagonists

Mirikizumab, risankizumab, guselkumab

• Binds to p19 subunit, which prevents p19 from attacking to IL-23 receptor

S1P antagonists

Ozanimod, etrasimod

• Work in lymphoid cells; prevent WBCs from going into blood vessels of colon

Vedolizumab

Integrin inhibitor:

• Prevents MAdCAM-1 from binding to T-lymphocytes

Azathioprine

Thiopurine / immunomodulator:

• Breaks down to active 6-mercaptopurine (6-MP) then to 6-TGN (active drug)

• Affects immune cells (T-cells, B-cells) and decrease inflammation

Methotrexate

Antifolate:

• Inhibits tetrahydrofolate (DHFR), which prevents TS from converting dUMP to dTMP (and then to dTTP), which then prevents dTTP for being used in DNA synthesis

Cyclosporine

Calcineurin inhibitor:

• Inhibits calcineurin, which inhibits transcription and translation that produces IL-2