The country's first anti-tumor new drug MDM2-p53 inhibitors entered the clinic.

On July 18, Jiangsu Yasheng Pharmaceuticals announced that its anti-tumor class 1 new drug MDM2-p53 inhibitor APG-115 has been approved by the State Food and Drug Administration (CFDA) to enter the Chinese clinic. It is reported that this is APG-115 in June 2016 after the FDA clinical approval made another significant progress, it is worth noting that this is the first in the country into clinical MDM 2-p53 inhibitors.
it is known that APG-115 is a small molecule inhibitor that is effective orally selective in the interaction of MDM2-p53 protein. P53 gene is the most widely studied tumor inhibition gene, p53 gene inactivation plays an important role in tumor formation, and MDM2 is one of the most important inhibitors of p53, when the two combine, will make p53 protein degradation, reduce activity, reduce cancer suppression. The design and development of new anti-tumor drugs with MDM2-p53 as the target is one of the hot spots and priorities in the field of global cancer drug research and development. However, due to the particularity of THE INTERACTION OF MDM2-p53 proteins, the development of small molecule inhibitors has caused considerable difficulties, resulting in the global field of research drugs in the few. There are no drugs on the market globally for this target, and domestic drugs in the field have not been reported otherwise except APG-115.Professor Wang Shaomeng, Chief Scientific Officer of Yasheng Pharmaceuticals,
, said that drugs targeting MDM2 targets are in the research and development stage, with Roche's Idasanutlin (RG-7388), Amin's AMG-232 and Novartis' HDM201. Compared with the above drugs, APG-115 has significant activity and drug benefits.
preclinical research data show that APG-115 can form effective inhibition of tumors such as sarcoma, primary liver cancer, primary stomach cancer, and animal testing can completely disappear tumor tissue. In addition, the combination of MDM2-p53 inhibitors with Bcl-2 selective inhibitors enhances tumor inhibition. Studies 2 have shown that the combined use of MDM2-p53 inhibitors and Bcl-2 inhibitors can produce strong synergistic anti-tumor effects in in vitro and in vivo models of acute myeloid leukemia (AML) compared to either of the two drugs.
because MDM2-p53 inhibitors are cell cycle-dependent, their induced effect on apoptosis is only apparent only after the cell has undergone at least two cycles, and Bcl-2 inhibitors remove this dependence, which accelerates the motivation of the cell death procedure. Roche is currently conducting clinical I studies of its MDM2-p53 inhibitors (idasanutlin/RG-7388) in conjunction with Bcl-2 inhibitors (venetoclax/ABT-199) for recurrent or refractive AML.
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