ENP Newswire -
Release date- 07082014 -
The compound, generated using computer-based virtual design and evaluation, inhibits the activity of cancer-causing protein (target protein).
In addition to the IT-based drug discovery of this new active compound, the research collaboration yielded multiple low-molecular-weight compounds that provide important information in advancing drug discovery research. The three parties have decided to pursue the optimization of the low-molecular-weight compounds generated by their research with the aim of moving forward to preclinical evaluation(1) of the compounds.
Based on RCAST's research on proteins thought to cause specific diseases, the research collaboration moved forward on two methods of drug discovery research targeting cancer indications. One method is IT-based drug discovery, while the other combines conventional low-molecular-weight drug discovery technologies with computer-based compound screening. In the IT-based drug discovery effort,
In addition, during this collaboration
Research Results to Date
With conventional low-molecular-weight drug discovery technology, researchers look for compounds that exhibit a certain threshold of inhibitory activity(2). They do this by screening a reagent company-supplied commercial library of existing low-molecular-weight compounds against a target protein. Development of the compounds identified by the screening to drug candidate compounds requires manipulation into a novel structure, but the problem has been that the method does not necessarily provide compounds suitable for the manipulation.
The current research collaboration, however, used drug candidate compound design technology(3). This technology leveraged a computer to design a variety of compound structures that would bind to the target protein. Those were then filtered using high-precision activity prediction technology(4) to predict their inhibitory activity. Afterwards, they were synthesized and their inhibitory activity was measured through assays. This method yields novel chemical structures that are not easily generated using conventional drug discovery techniques involving manipulation of known compounds. The aim was to generate, with a high degree of probability, drug candidate compounds with potent inhibitory activity.
The collaborative efforts produced a variety of computer-designed chemical structures, of which 22 were selected on the presumption that their interaction with the target protein would lead to the formation of a stable complex structure with the target protein. Eight of those compounds were then synthesized and their inhibitory activity was measured in assays. Of these, one low-molecular-weight compound showed inhibitory activity that met the target threshold, representing the successful generation of a new active compound. Accordingly, the rate of one in eight compounds, or 12.5%, is a much higher ratio than conventional low-molecular-weight drug discovery technologies yield.
In addition to the IT-based drug discovery of a novel active compound, the research collaboration of RCAST,
Next Stage in the Research Collaboration
Overview of the Research Collaboration
Respective Responsibilities: RCAST: Provision of information on proteins thought to cause specific disease indications
 Preclinical evaluation
A phase of drug development in which studies are conducted prior to clinical testing in human subjects. These studies test safety and efficacy in animals.
 Inhibitory activity
The degree to which a compound binds to a protein thought to cause a specific disease indication and inhibits the function of the protein. Usually expressed in terms of the concentration of the compound.
 Drug candidate compound design technology
Optimum Packing of Molecular Fragments (OPMF), a software module developed by
 High-precision activity prediction technology
Software developed by
Global sales of the company's flagship product, pitavastatin (known as LIVALO and LIVAZO in different markets) was over
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