The phosphatidylinositol 3-kinase (PI3K) alpha inhibitor CYH33, jointly developed by the Shanghai Institute of Materia Medica and Chinese Academy of Sciences, has recently received the implicit permission for clinical trials (IND) from the US Food and Drug Administration (FDA). It is used to treat advanced solid tumors.
The dysregulation of PI3K signaling pathway involves most human cancers. PIK3CA (encoding PI3K catalytic subunit α) is one of the common mutant oncogenes in human tumors. About 2-5% of human solid tumors have mutations in the oncogene PIK3CA, involving Tumor types such as breast cancer, ovarian cancer, colon cancer, glioblastoma, lung cancer and esophageal cancer.
CYH33 is a new, highly efficient and specific PI3Kα inhibitor jointly researched and developed by Shanghai Pharmaceutical Institute and Haihe Biology. By inhibiting the PI3K-mediated signaling pathway, it blocks cells in the G1 phase, thereby inhibiting tumor cell proliferation. Yang Chunhao's research group of Shanghai Institute of Pharmaceutical Sciences used the synthetic methodology developed by itself to introduce the pyrrolotriazine mother core of the medicinal chemistry into the PI3K inhibitor for the first time. Through the systematic structure-activity relationship study, he and the Ding Jian team worked together to discover Candidate drug CYH33. Preclinical studies have shown that CYH33's in vivo and in vivo activity is superior to the similarly marketed drug BYL719.
The clinical research carried out by CYH33 has shown that the compound has good safety and preliminary clinical efficacy. At present, there is no selective PI3Kα inhibitor approved in China.