Brostallicin

Brostallicin is a new class of cancer drug — a synthetic DNA minor groove binding agent. Most cytotoxic agents bind DNA’s major groove, have little sequence-specificity, and are severely toxic to normal tissues (including topoisomerase inhibitors, such as camptothecins and anthracyclines).

DNA minor groove binders such as brostallicin possess high affinity and selectivity for interaction with DNA. All minor groove binders bind to the same DNA structure; however, brostallicin has a unique and very interesting mechanism of action.

Brostallicin binds to DNA only in the presence of glutathione (GSH) and glutathione S-transferase (GST) which are overexpressed in cancer cells but not in normal cells, conferring upon brostallicin a novel and highly selective mechanism of action superior to other minor groove binding agents.

By binding to the minor groove, brostallicin provides a new target to interfere with DNA division and lead to tumor cell death. Brostallicin is potently synergistic in combination with standard cytotoxic agents as well as newer targeted therapies.

Brostallicin has a unique ability to become more active in tumors that are resistant to other cancer drugs. Its anti-tumor activity remains high in the presence of a number of critical cancer causing genetic abnormalities that cause resistance to standard anti-cancer agents. This activity profile makes it of extreme interest in designing trials to test its activity in targeted patients with certain genetic abnormalities.

Brostallicin Clinical Research