Cdc7(AS-0141)

Indication

Small molecule compound is the form which has been used for the conventional drugs, but will still be one of the major types of drugs because of the following strengths:

• It can target intracellular targets by its permeability to the cellular membranes.
• It can restrict the drug expenses as it is generally affordable by mass production.
• There is huge accumulation of know-hows for the drug development.

Meanwhile, small molecules are often noted for the drug toxicity. Many of the conventional small molecule drugs, especially which are targeted for the rapidly growing cells, are notorious for its effect on the proliferating normal cells, such as hair follicle cells, skin cells, or blood stem cells.

Mode of action

Before the cells divide, it is needed to have the nucleic DNA to be newly synthesized (replication) during the S-phase (S stands for synthesis). Cdc7 kinase is known to activate MCM protein complex, which is inevitable for the commencement of DNA replication. If Cdc7 kinase activity is blocked at this point, the DNA replication is incompletely suspended.

In the cell division steps, there are checkpoints which allow the procession of the cell division processes after the confirmation of proper DNA replication, but such systems are often devastated in cancer cells, which results in uncontrolled proliferation of the cells. When such cancer cells are challenged with Cdc7 inhibitors, the resultant incomplete DNA replication leads to the genomic catastrophe and eventually kills the cancer cells.
Meanwhile, under the presence of Cdc7 inhibitor, the normal cells are temporarily halted with the cell division due to incompletely replicated DNA. However, the DNA is still repairable and the cell division will start over when the inhibitor is washed away.

Thus the Cdc7 inhibitors are expected to be the novel anti-cancer drugs that specifically kill cancer cells without major effect on normal cells. In addition, they are considered to be effective against various cancers as Cdc7 is often strongly expressed broadly among various cells.