JNJ-4355

JNJ-4355 is a highly potent and selective small molecule inhibitor of Myeloid Cell Leukemia-1 (MCL-1), developed by Janssen Research and Development for the treatment of hematological malignancies. Chemically characterized as a 1,4-indolyl macrocycle, JNJ-4355 functions by disrupting the protein-protein interaction between MCL-1 and pro-apoptotic BH3-only proteins (such as BAK), thereby inducing mitochondrial outer membrane permeabilization (MOMP) and subsequent apoptosis in cancer cells. The molecule was optimized to address the physicochemical limitations of first-generation MCL-1 inhibitors, demonstrating improved solubility and reduced protein binding. Preclinical studies have shown significant efficacy in acute myeloid leukemia (AML) and multiple myeloma models, including complete tumor regression in xenograft studies following a single intravenous dose.