New Drug Slows Lung Cancer Growth in Mouse Model

Drug developers have formulated a new class of platinum-based chemotherapeutic agents that when tested in an animal model for non-small cell lung cancer (NSCLC) proved to be 10 times more effective than existing treatments. Currently, less than one-third of non-small cell lung cancer patients respond to traditional platinum-based therapies, and those who do respond have a median survival of less than a year.

Investigators from Wake Forest University (Winston-Salem, NC, USA) worked with a dual platinating/intercalating DNA binder that, unlike clinical platinum agents, does not induce DNA cross-links. This compound has the long chemical formula [PtCl(Am)2(ACRAMTU)](NO3)2, where (Am)2 = ethane-1,2-diamine, en; ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea).

The investigators reported in the December 11, 2008, issue of the Journal of Medicinal Chemistry that by substituting an amidine group for the thiourea they were able to greatly enhance the cytotoxicity of the drug against NSCLC in vitro and in vivo. The new compound slowed tumor growth in an H460 mouse xenograft study by 40% when administered at a dose of 0.5 mg/kg.

"We are able to slow the growth of this cancer substantially in mice,” said senior author Dr. Ulrich Bierbach, associate professor of chemistry at Wake Forest University. "That is very good news, since this is such a rapidly growing, intractable type of cancer. If this ends up in clinical trials in the next few years, that will fulfill a dream of mine.”

Related Links:
Wake Forest University