4-methyl itaconate

4-methyl itaconate (4-MI) is a cell-permeable monoester derivative of itaconate, an endogenous anti-inflammatory metabolite synthesized by macrophages. It functions as an immunomodulator by activating the Nuclear factor erythroid 2-related factor 2 (NRF2) antioxidant pathway and inhibiting the activation of the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome. These actions lead to the downregulation of proinflammatory cytokines, including interleukin-6 (IL-6), interleukin-1β (IL-1β), and interferon beta (IFNβ). In preclinical studies, 4-MI has demonstrated the potential to treat alopecia areata by suppressing the autoimmune disruption of hair follicles and promoting the transition from the telogen to the anagen phase of the hair cycle. Due to its limited skin permeability, 4-MI is often delivered via lipophilic prodrugs such as SCD-153 for topical application. The development of 4-MI and its derivatives involves a collaboration between Johns Hopkins University, Sun Pharma Advanced Research Company (SPARC), and the Institute of Organic Chemistry and Biochemistry (IOCB) of the Czech Academy of Sciences.

Other names

4-methyl itaconatemonomethyl itaconate4-MI