limantrafin

Limantrafin (formerly CB-103) is a first-in-class, orally bioavailable small molecule inhibitor of the Notch signaling pathway. Unlike gamma-secretase inhibitors (GSIs) that prevent Notch receptor cleavage, limantrafin targets the Notch transcription complex (NTC) directly by disrupting the protein-protein interaction between the Notch intracellular domain (NICD) and the DNA-binding protein CSL (RBPJ). This downstream inhibition blocks the assembly of the active transcriptional complex, thereby suppressing the expression of Notch target genes involved in cell proliferation and survival. Limantrafin is being developed for Notch-driven malignancies, including T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL), where it is often studied in combination with other targeted therapies like venetoclax to overcome resistance and enhance efficacy.

Other names

6-(4-(1,1-dimethylethyl)phenoxy)-3-pyridinamine3-pyridinamine, 6-(4-(1,1-dimethylethyl)phenoxy)-