At the 89th Annual Meeting of the American Association for Cancer Research, BioNumerik Pharmaceuticals, a company based in San Antonio, Texas, presented the promising results of its preclinical studies on the antitumour activity of two supercomputer engineered small molecule agents, referred to as Karenitecins and BNP7787. The strong correlation between actual experimental observations and the computational simulations, performed through innovative supercomputer programming and mechanism based approach, are paving the way to creative and inspiring pharmaceutical discovery and development.
Karenitecins constitute a novel class of highly lipophilic or fat loving camptothecins. When orally administered, they display a superior anticancer activity, fighting solid tumours affecting organs, such as the prostate, colon, breast and lung. They even demonstrate the ability to bypass common drug resistance mechanisms in contrast with other water soluble camptothecins. Because of their lipophilic structure, they tend to easier penetrate tissue, resulting in optimised drug delivery and bio-availability. The BioNumerik company has succeeded in creating a detailed computational agent model by means of its Cray supercomputers. The researchers introduced human Topoisomerase I and DNA, enabling them to precisely observe the key interactions between camptothecin and Topo I/DNA. This basic information led them to discover and refine new elements for laboratory synthesis and preclinical testing.
The second agent, BNP7787, is a water soluble disulfide, especially engineered to enhance the therapeutic influence of cisplatin and carboplatin, which constitute the two major anticancer drugs. Unfortunately, both these drugs execute a negative effect with regard to kidney toxicity, nausea and vomiting, bone marrow suppression, and neurotoxicity. The BioNumerik research team now has found however that a slight dose of BNP7787 substantially reduces the toxic activity of the platinum drug species while at the same time, increasing the antitumour power of platinum chemotherapy. In other words, BNP7787 should allow doctors to safely administer higher and more effective doses of cisplatin and carboplatin to cancer patients in the future, in order to obtain higher patient response outcomes.
Currently, BNP7787 is passing through Phase I of a series of clinical trials at the University of Chicago Medical Centre, at the Roswell Park Cancer Institute, at the Johns Hopkins Oncology Centre, as well as in Europe, at the Free University Hospital in the Netherlands. To perform its pioneering cancer research, BioNumerik Pharmaceuticals follows an interdisciplinary approach, integrating medicine, quantum physics, synthetic chemistry, pharmaceutical sciences and powerful Cray supercomputing programmes to generate a fourth generation technology with regard to drug screening. Only this way of proceeding can guarantee a timely introduction of new anti-cancer drugs for clinical development.