PhiKan 083, a Potent p53 Mutant Stabilizer for Cancer Research

PhiKan083 p53 Mutant Stabilizer Cancer Apoptosis 2019 04 11 - PhiKan 083, a Potent p53 Mutant Stabilizer for Cancer Research

Tumor suppressor p53 is an important protein in cells. It regulates cell cycle, apoptosis and genomic stability. Most mutation of p53 is inactive in half of human cancers. Mutant p53 also leads to the rapid denaturation of the protein. Therefore, it is necessary to find out an activator binding to the mutant p53 and stabilizing them. Then, the compound may have potential in cancer therapy. PhiKan 083, a potent p53 mutant stabilizer proves to be such a compound.

How does the product act on p53?

Researchers find out, PhiKan 083 can bind to p53-Y220C. The later is a common mutant form of p53. PhiKan 083 binds to the surface cavity, and stabilizes Y220C, with a Kd of 167 μM.

Since PhiKan 083 has such reasonable affinity at p53-Y220C, it should be further studied.

Cellular assays are carried out for measuring the bioactivity of PhiKan 083. It exhibits significant anti-tumor effect. PhiKan 083 (125 μM) reduces the cell viability of engineered variants of
Ln229 cells. The cells are a kind of glioblastoma cells. Moreover, PhiKan 083 (100 μM) combined with doxorubicin (1 μM) enhances the pro-apoptotic activity in all variants of Ln229 cells (p53wt, p53Y220C, p53G245S, p53R282W).

Considering the efficacy of PhiKan 083, researchers need to go on further study to explore the potential of the stabilizer. Hope PhiKan 083 will play a vital role in cancer treatment.