Design and Catalyzed Activation of Tak-242 Prodrugs for Localized Inhibition of TLR4-Induced Inflammation.

Tak-242 (resatorvid), a Toll-like Receptor 4 (TLR4) inhibitor, has been identified as a potent suppressor of innate inflammation. As a strategy to target Tak-242 to select tissue, four TLR4-inactive prodrugs were synthesized for activation via two different release mechanisms. Two nitrobenzyl Tak-242 prodrugs released the parent drug upon exposure to the exogenous enzyme nitroreductase, while the two propargyl prodrugs were converted to Tak-242 in the presence of Pd0. Copyright © 2020 American Chemical Society.

Citation

Michael A Plunk, Alyssa Alaniz, Olatunde P Olademehin, Thomas L Ellington, Kevin L Shuford, Robert R Kane. Design and Catalyzed Activation of Tak-242 Prodrugs for Localized Inhibition of TLR4-Induced Inflammation. ACS medicinal chemistry letters. 2020 Feb 13;11(2):141-146

PMID: 32071680

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