Discovery of Orally Available Prodrugs of Itaconate and Derivatives

January 2025 in “ Journal of Medicinal Chemistry ”

Chae Bin Lee, Ivan Šnajdr, Lukáš Tenora, Jesse Alt, Sadakatali S. Gori, Marcela Krečmerová, R. Michael Maragakis, James Paule, Sandhya P. Tiwari, Jitesh Iyer, Rashmi Talwar, Luis A. Garza, Pavel Majer, Barbara S. Slusher, Rana Rais

itaconate prodrugs endogenous immunomodulator inflammatory cytokines human epidermal keratinocytes skin disorders

Studysummary This study identified orally available itaconate derivatives that improve cellular permeability and bioavailability, with specific POC-based prodrugs showing significant inhibition of inflammatory cytokines in human epidermal keratinocytes and favorable oral pharmacokinetics, highlighting their potential for treating systemic and skin disorders.

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