DNA damage is an abnormal chemical structure in DNA, it undergoes DNA repair. DNA repair is a process to identify and correct DNA damage. If the process fails, irreparable DNA damage may happen. Consequently, this may lead to malignant tumors.
ATAD5 (ATPase family AAA domain-containing protein 5) is a protein, involves in DNA damage response. Once DNA damage occurs, ATAD5 exhibits increased levels, but with no obvious changes of its mRNA transcription. Therefore, inhibition of ATAD5 may play a vital role in the treatment of cancer diseases.
Researchers carried out a quantitative high throughput screening assay to explore the promising compound. And herein, we will talk about ML367 as an inhibitor of ATAD5 stabilization.
ML367 is a probe molecule, exhibits low micromolar inhibitory activity against ATAD5 stabilization. It also suppresses general DNA damage responses, such as phosphorylation of RPA32 and CHK1 in response to UV irradiation. This demonstrates ML367 has the potential in blocking DNA repair pathways.
In addition, ML367 displays excellent activity in the following assays. The inhibitor inhibits ATAD5 stabilization and causes destabilization of the protein in HEK293T cells. Moreover, it blocks the growth of cells that lack DNA damage repair proteins.
ML367 also has other advantages, including good PAMPA permeability, stability and biological activity.
ML367 is an inhibitor of ATAD5 stabilization. The combination of ML367 with inhibitors of DNA repair proteins may have the potential role in cancer therapy.
References:
1. Rohde JM, et al. Probe Reports from the NIH Molecular Libraries Program.