ScholarWorks@중앙대학교

초록

Janus kinases (JAKs) mediate cytokine and growth factor signaling by phosphorylating STAT proteins, playing a critical role in immune regulation. Among JAK family, JAK2 drives hematopoietic and immune signaling. Its dysregulation promotes myeloproliferative neoplasms (MPN) by impairing hematopoietic stem cell function. Selective JAK2 inhibition offers a promising therapeutic strategy for effective and safe MPN treatment. Starting from a non-selective JAK inhibitor, we synthesized a series of furopyrimidine derivatives to discover potent, JAK2-selective inhibitors. Structural optimization led to potent JAK2 inhibitors with improved selectivity. Further refinements led to compound 14, which exhibited approximately 10-fold selectivity for JAK2 over JAK1 and negligible inhibition of JAK3 and TYK2 in biochemical assays. These findings provide a framework for designing novel JAK2-selective inhibitors with improved potency and specificity for MPN therapy.

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