Yissum Ltd. has announced that scientists from the School of Pharmacy at the Hebrew University of Jerusalem discovered a novel orally available drug that prevents metastasis formation in various types of cancers.
The novel drug is a small molecule named cis-ACCP, which is a prototype of a family of compounds that may be administered orally and was shown as highly effective in rodents without inducing any adverse side-effects. The development of the drug was a collaborative effort of the laboratories of Prof. Eli Breuer, Prof. Reuven Reich and Prof.
Amnon Hoffman, all from the School of Pharmacy at the Hebrew University of Jerusalem. The work was published in the Journal of Medicinal Chemistry.
Nava Swersky Sofer, Yissum's President and CEO, stated, "This new class of drugs could potentially change the lives of millions of cancer patients by providing protection from metastasis in the form of a pill. Of course, many years of testing are ahead of us before the drug can reach the patients, but this is the first step."
cis-ACCP, the novel drug, inhibits enzymes called matrix metalloproteinases (MMPs), which are extracellular enzymes known to play a crucial role in physiological tissue remodeling and repair.
However, pathological over-expression of MMPs has been associated with a variety of chronic diseases including cancer, arthritis, osteoporosis, multiple sclerosis, arteriosclerosis, congestive heart failure, chronic obstructive pulmonary disease, liver cirrhosis, and others. In cancer, over-expression of MMPs enables the tumorigenic cells to invade other tissues, leading to metastasis formation. In most cases, this is a turning point that renders the tumor untreatable by conventional treatments.
The efficient inhibition of MMPs is therefore an important therapeutic target that has attracted considerable attention within the research community for the last two decades. Yet, in spite of the huge effort devoted to this goal, no clinically useful inhibitor has been developed to date. The main obstacles encountered by scientists trying to develop such inhibitors were high toxicity leading to unacceptable side-effects, and low bioavailability since most of the potential drugs were not soluble in water and hence could not effectively reach the extracellular fluid, where their target proteins are found.
In contrast, cis-ACCP, has a very low toxicity as revealed by preclinical trials on rodents. This is achieved via two important properties of the drug: it inhibits the activity of selected MMPs without inhibiting similar proteins; and due to its hydrophilic (water-soluble) nature, the drug does not enter the cells, but rather stays in the extracellular fluid, where it exerts its effect. In other words, cis-ACCP is self-targeted to its appropriate site of action, namely outside cells, which reduces potential intracellular toxicities.
The preclinical experiments described in the paper also showed that the novel drug prevents cancer cells from invading adjacent tissues (and thus forming metastases), and is effective in treating melanoma (skin cancer) and prostate cancer in rodent model systems.
The results showed that cis-ACCP significantly inhibited both tumor growth and metastasis formation.