Zhang Kehui; Xu Heng; Lin Songwen, PhD; Chen Xiaoguang; JI Ming, PhD
Competition Sponsor: Chinese Academy of Medical Sciences
Glioblastoma is the most common primary intracranial tumor caused by the carcinogenesis of glial cells in the brain and spinal cord. It is highly aggressive, recurs easily, and has limited treatment options. Currently, only Temozolomide (TMZ) has been approved by the FDA for clinical use, which, however, shows obvious side effects and severe drug resistance after long-term use. Therefore, the development of new anti-glioma drugs is imminent. PI3K inhibitors not only have superior anti-tumor activity by selectively blocking the signal pathways involved in tumor cell proliferation, but also reduce the incidence of drug resistance. Based on our previous research, in this project, we have developed a new structure of the blood-permeable brain barrier PI3K inhibitor drug candidate XH-30. The candidate drug has good blood-brain barrier permeability, strong target inhibitory activity and high selectivity. It has high antiproliferation activities against a variety of glioma cells, and is used in subcutaneous and in vivo models of glioma, in which XH-30 can both almost completely inhibit the growth of tumors and has good safety profile. In view of the good pharmaceutical properties of the candidate drug, we are planning to carry out systemic preclinical studies of XH-30 in this project, including pharmacology, pharmacology, pharmacokinetics, and toxicology studies. The goal will be to obtain clinical trial permission from the State Food and Drug Administration of China to carry out clinical research of the drug to meet the huge clinical needs.