Azathioprine

Category: pharmacological

Aliases: Imuran

Pharmacological Mechanism

Prodrug of 6-mercaptopurine — incorporated into DNA as thioguanine nucleotides causing immunosuppression. TPMT polymorphism (~10% intermediate, ~0.3% deficient) drives marked toxicity variability — pre-treatment TPMT/NUDT15 genotyping standard. IBD + autoimmune + steroid-sparing transplant maintenance.

Half-Life (t½)

PO: 5h

Dosing Guidelines

• PO: Typical 150 mg (Range: 50–200 mg)

Target Organ Systems

• digestive
• immune-hematologic

Pathways It Modulates

• Calcineurin / NFAT T-cell activation (inhibitor) — purine synthesis (downstream of T-cell activation)
• CD4 T-helper differentiation (inhibitor) — purine synthesis → lymphocyte anti-proliferative
• cGAS-STING cytosolic DNA sensing → type I IFN (inhibitor) — broad anti-lymphocyte (downstream IFN-driven processes)
• DNA-damage cytotoxic chemotherapy (inhibitor) — 6-MP prodrug → de novo purine synthesis + DNA incorporation

Chemical Identifiers

• PubChem CID: 2265
• Formula: C9H7N7O2S
• Molecular weight: 277.26 g/mol
• InChIKey: LMEKQMALGUDUQG-UHFFFAOYSA-N
• SMILES: CN1C=NC(=C1SC2=NC=NC3=C2NC=N3)[N+](=O)[O-]

References

• PMID 8881811