JNJ-54452840

JNJ-54452840 is an investigational small molecule inhibitor of p38 mitogen-activated protein kinase (MAPK), specifically targeting the alpha isoform (MAPK14). Developed by Janssen Research & Development, it was primarily evaluated for the treatment of dilated cardiomyopathy (DCM) associated with mutations in the Lamin A/C (LMNA) gene. In LMNA-related DCM, the p38 MAPK pathway is chronically overactivated, contributing to cardiac dysfunction, adverse remodeling, and progression to heart failure. By inhibiting this pathway, JNJ-54452840 aimed to mitigate pathological cardiac signaling and improve myocardial function. Clinical development reached Phase 1/2 trials; however, Janssen terminated the program in 2021.