molecules of the month

Compound 4e

inhaled p38α/β MAPK inhibitor

effective in the rat LPS-induced lung inflamm. model

SBDD and focus on slow dissociation kinetics

J. Med. Chem.

Chiesi Farmaceutici, Parma, IT

Compound 4e Chemical Structure, inhaled p38α/β MAPK inhibitor - Chiesi Farmaceutici, Parma, IT
4 mins read

Context. “compound 4e” (Chiesi Farmaceutici) is an inhaled p38α/β mitogen-activated protein kinase (MAPK) inhibitor being developed for lung inflammatory diseases. As a regulator of key proinflammatory mediators, p38 MAPK has been extensively explored as a therapeutic target for inflammatory diseases, including those of the lung. However, despite the description of the first p38 MAPK inhibitor nearly 3 decades ago, no agent has been approved targeting the protein, likely attributable to selectivity and/or tolerability issues. Regardless, the pursuit of these inhibitors has not waned and more than 20 candidates are currently in various stages of clinical development, the most advanced of which is Fulcrum Therapeutics’ losmapimod which, although failed in chronic obstructive pulmonary disease (COPD) trials, is seeing some success in…

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