A 58-year-old woman with long-standing seropositive rheumatoid arthritis has failed methotrexate and sulfasalazine. She is started on a JAK inhibitor. Which intracellular signaling pathway is primarily targeted by this class of drugs?

• A NF-kB pathway
• B PI3K-AKT pathway
• C MAP kinase pathway
• D JAK-STAT pathway ✓

Explanation

Janus kinase (JAK) inhibitors such as tofacitinib, baricitinib, and upadacitinib block the JAK-STAT intracellular signaling pathway. This pathway is used by multiple pro-inflammatory cytokines (including IL-6, IL-12, IL-23, and interferons) to transmit signals from cell surface receptors to the nucleus, thereby reducing inflammatory gene transcription. The other pathways are not the primary targets of JAK inhibitors.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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