TMC-Ag3 + TMC-Ag5

TMC-Ag3 + TMC-Ag5 is a preclinical combination therapy developed by Arjuna Therapeutics for the treatment of solid tumors, specifically intended for use in conjunction with radiotherapy or radioligands. This therapy utilizes Therapeutic Molecular Clusters (TMCs), a novel class of small molecule drugs consisting of defined arrangements of silver atoms. TMC-Ag5 (containing five silver atoms) irreversibly inhibits the glutathione (GSH) and thioredoxin (Trx) antioxidant pathways, leading to the amplification of reactive oxygen species (ROS) and selective apoptosis in cancer cells with high oxidative stress. TMC-Ag3 (containing three silver atoms) targets topoisomerase-DNA complexes, acts as a DNA intercalator, and modulates chromatin accessibility to enhance the efficacy of DNA-damaging agents. The combination is designed to synergistically increase tumor cell death by pairing antioxidant defense inhibition with direct DNA targeting. These clusters are highly stable, orally bioavailable, and capable of penetrating solid tumors and crossing the blood-brain barrier.

Other names

TMC Ag3 + TMC Ag5-Arjuna Therapeutics-GSH (glutathione) antioxidant pathway-Trx (thioredoxin) antioxidant pathway-Reactive oxygen species (ROS) amplification-Topoisomerase–DNA complex-DNA (intercalation)-Chromatin accessibility-Therapeutic Molecular Cluster (TMC) combination therapy-Solid tumors (in combination with radiotherapy or radioligands)