Potentially More Patient-Friendly

Brostallicin (bräst-al-iss-in) is a small molecule, chemotherapeutic agent with a unique mechanism of action. Data in more than 230 patients treated in phase I/II clinical trials reveal evidence of activity in patients with refractory cancer and patient/physician-friendly dosage and administration. Brostallicin may ultimately be useful in combination with newer, targeted cancer therapies as well as established treatments for common tumor types.

A New Class of Cancer Drug

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.

A Novel and Unique Mechanism of Action

Brostallicin binds to DNA only in the presence of glutathione (GSH) and glutathione S-transferase (GST), which are produced to a greater extent in cancer cells than in normal cells.

This gives brostallicin a novel and highly selective mechanism of action that is superior to other minor groove binding agents.

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

High Anti-Cancer Activity

Brostallicin has a unique ability to retain activity in tumors that are resistant to other cancer drugs. Additionally, 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, such as mismatch-repair mutations in inherited breast, ovarian, and colorectal cancers that are generally resistant to treatment.

Brostallicin Clinical Research

We are currently studying brostallicin in a phase II trial as a single agent for patients with advanced or metastatic soft tissue sarcoma, and in a context of vulnerability trial in several patient populations.