Darinaparsin (Zinapar™ or ZIO-101) is a novel mitochondrial-targeted agent (organic arsenic) being developed intravenously for the treatment of relapsed peripheral T-cell lymphoma likely with a two-stage potentially pivotal study expected to begin in late 2011. An oral form is in a Phase I trial in solid tumors.



Arsenic has been used to treat cancer for more than 2000 years. Concepts of modern chemotherapy derive from early 20th century studies of arsenic when it was a mainstay of cancer chemotherapy. For example, in the early 1930s, inorganic arsenic was used to treat chronic myelogenous leukemia (CML) with dramatic effects.

Inorganic arsenic (such as arsenic trioxide) has diverse effects on many tissues including the heart and cardiovascular system, gastrointestinal tract, kidneys, skin, nervous system, and blood and bone marrow. Inorganic arsenic is especially toxic to the liver, causing infiltration, central necrosis, and cirrhosis. Furthermore, inorganic arsenic causes cancer of the skin and lung in humans. When given at high doses, inorganic arsenic has also been associated with EKG abnormalities.

Unlike inorganic arsenic, preclinical and clinical studies show little serious toxicities associated with organic arsenic.

In vitro and in vivo testing in a leukemia animal model demonstrated substantial activity against hematological cancers (cancers of the blood). These include leukemia, lymphoma, myelodysplastic syndromes and multiple myeloma.

Additionally, in vitro testing of darinaparsin (ZIO-101) detected activity against lung, colon, brain, melanoma, ovarian and kidney cancer. Moderate activity was detected against breast and prostate cancer.