LXG6403 / Loxigen - LARVOL DELTA

A highly potent bi-thiazole inhibitor of LOX rewires collagen architecture and enhances chemoresponse in triple-negative breast cancer. (PubMed, Cell Chem Biol) - "Structure-activity relationship analysis identified a potent lead compound (LXG6403) with ∼3.5-fold specificity for LOX compared to LOXL2 while not inhibiting LOXL1 with a competitive, time- and concentration-dependent irreversible mode of inhibition...This leads to better drug penetration, inhibits FAK signaling, and induces ROS/DNA damage, G1 arrest, and apoptosis in chemoresistant triple-negative breast cancer (TNBC) cell lines, PDX organoids, and in vivo. Overall, our potent and tolerable bi-thiazole LOX inhibitor enhances chemoresponse in TNBC, the deadliest breast cancer subtype."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • LOX

Rewiring collagen architecture using a highly potent bi-thiazole inhibitor of LOX mediates chemosensitization in triple-negative breast cancer (AACR 2024) - "Structure-activity relationship analysis further identified a potent and relatively LOX-specific lead compound (LXG6403) that reduces collagen content and crosslinking, and fibronectin assembly, leading to increased chemoresponse in triple-negative breast cancer (TNBC) cell lines and PDX organoids in 3D collagen...This leads to better drug penetration, inhibition of FAK signaling, and induction of ROS generation/DNA damage, leading to G1 arrest and apoptosis in chemoresistant TNBC PDXs. Overall, our novel, potent, tolerable bi-thiazole LOX inhibitor enhances chemoresponse in TNBC, the deadliest breast cancer subtype."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • LOX