US researchers have discovered that by modifying a long-standing drug used to treat serious parasitic diseases like malaria, they could get it to affect human proteins in a way that looks promising for the treatment of cancer and immune-related diseases.

One of the researchers, Dr. Gregory Poon, a pharmaceutical scientist at Washington State University (WSU), says of their discovery:

“This was rather unexpected, given how relatively simple the molecules are that we modified and how difficult it has been to affect these proteins.”

He and his colleagues write about their findings in a recent online issue of the journal Nucleic Acids Research.

There they descibe how with simple modifications, they could get the drug furamidine to alter human proteins that switch certain genes on and off.

The modified furamidine was able to alter a group of human proteins known as transcription factors. These orchestrate the highly intricate sequences of gene expression that make cells function, and they are attractive targets for therapeutic drugs for the treatment of cancer and immune-related diseases.

Until now, it has been very difficult to design drugs that target transcription factors, and for this reason, says Dr. Poon, they have been called “undruggable.” He adds:

Recently, however, scientists have been making headway in targeting these transcription factors with drugs, and now our results suggest this class of drugs can be a useful addition to the arsenal.”

Furamidine, which belongs to a family of drugs known as heterocyclic dications, has long been used to treat serious parasitic diseases, such as malaria, African sleeping sickness and PCP – a serious infection that often affects people with HIV and AIDS.

Such a long history means we have gathered a lot of knowledge and experience about the use furamidine and its relatives in humans, says Dr. Poon, “so these drugs have an important advantage over other classes of drugs that are relatively behind in clinical experience.”

In their study, the team found that modified versions of furamidine can target a specific transcription factor known as PU.1, which plays a key role in how the immune system develops and functions. It also plays a major role in diseases, including certain leukemias, multiple sclerosis and diabetes.

PU.1 is part of a large family of transcription factors known as ETS, which are involved in many cancers and other diseases.

Dr. Poon says:

The challenge now is to fine-tune this class of drugs to make them as specific as possible to other ETS-family transcription factors as well.”

Funds from the WSU College of Pharmacy and the National Institutes of Health at Georgia State University helped finance the study.

In another recent study that found a new use for an old drug, researchers revealed how a common high blood pressure drug could enhance cancer treatment.