Focus on the outcome(phenomenon) of G2 checkpoint abrogation

Many of phenomena developed in living cells are emerging through signal transduction pathways with various molecular groups complicatedly entangled. Most of those signal pathways have not been clarified.

The signal transduction pathway associated with G2 checkpoint is also one of them; there has been no clinical study reported as of now to evidence the efficacy of a drug agent to abrogate G2 checkpoint specifically by inhibiting functions of specific molecular.

In many cases of drug screening, "high throughput screening" (technology of high speed analysis for the activity of compound to single or a few specific target molecule(s) ) is performed as the first step to screen "deviant" from a large quantity of candidate compounds at early stage. However, this approach is not easy to apply for the field with unspecified target molecules, including G2 checkpoint abrogation.

In contrast, our screening method is to focus on behaviors associated with cell cycles of living cells, rather than the activity of specific target molecules.

Our unique method of drug screening on the basis of cell behavior as the final output does not require pre-specified target molecules, but is applicable with complicated or even unknown signal transduction pathways.

We believe that our drug screening method is effective in the field of G2 checkpoint with a lot of unclarified parts. All of our drug pipelines of candidate compounds have been explored and discovered by this drug screening method.

Because the method employs living cells, automation is difficult, and therefore, there is a disadvantage to improve the throughput easily.However, that serves conversely as a barrier for other pharmaceutical and/or drug development companies that generally pursue higher throughput to mimic or follow our technique.In the meanwhile, in order to overcome the disadvantage, we utilize some drug discovery support tools including data mining technology to improve the throughput of our unique screening method.

Compounds obtained through our screening method

As described above, we explore and optimize compounds, with the same phenomenon (not to have cancer cells stay in cell cycle G2 phase but apoptosis, while no impact on normal cells) occurred at abrogation of G2 checkpoint as indicator.

However, this same phenomenon might be observed even not at "G2 checkpoint abrogation" in the strict sense.
One of such examples is the case to shorten the time to remain in G2 phase without inhibiting G2 checkpoint function.

Therefore, "G2 checkpoint abrogation" is not pronounced only with phenomenon.
In addition, generally, many of successful compounds have low activity and cannot act as pharmaceuticals in living body as is. Therefore, in order to obtain expected activity in vivo, structure of those compounds have been modified for "optimization".During that process, improvement / modification to increase the activity without enhancing adverse drug reactions may develop anticancer activity by unknown (consequently, possibly different from G2 checkpoint abrogation) mechanism of action.
For this reason, we do not call pipeline compounds obtained from our screening method as "G2 checkpoint abrogation."

Nevertheless, these pipelines are nothing different from the one we have tried to obtain, i.e., "candidates of anticancer drug with fewer impact on normal cells as well as fewer side effects". Therefore, we believe them still meaningful compounds to develop as anticancer drug.