金年会

EZH1 or EZH2 is the catalytic subunit of the epigenetic regulatory factor PRC2 complex, responsible for the H3K27 methylation process, causing the expression of the corresponding gene to be silenced. Certain tumors and immune cells use EZH2 to promote tumor generation and progression and inhibit the response to anti-tumor drugs. For example, in follicular lymphoma, diffuse large B-cell lymphoma, multiple myeloma and other tumors, EZH2 often has gain-of-function mutations, which is a driving factor for tumorigenesis; Overexpression of EZH2 in a variety of solid tumors such as breast cancer, ovarian cancer, lung cancer, prostate cancer, and liver cancer is highly correlated with tumor occurrence, invasion, migration and poor prognosis; The tumors in which loss-of-function occurs in chromatin remodeling complex SWI/SNF or histone deubiquitinating enzyme BAP1 will also overly rely on the activity of PRC2. These tumors are sensitive to EZH2 inhibitors. Moreover, immune cells in the tumor immune microenvironment express EZH2 at high levels, which is an important mechanism for tumor immune escape. More and more evidence shows that EZH1 and EZH2 compensate each other in a variety of tumors. Therefore, simultaneously targeting EZH1/2 has the potential to treat a variety of malignant tumors. At present, there are not many small molecules targeting the PRC2 complex worldwide, and most of them are selective inhibitors of EZH2. Usually these molecules have poor pharmacokinetic properties.

HH2853 is a new, highly-effective and specific EZH1/2 dual inhibitor jointly researched and developed by Haihe Biopharma and Shanghai Institute of Meteria Medica. Systematic non-clinical studies have shown that HH2853 has excellent anti-tumor activity in vivo and in vitro, good pharmacokinetic properties and excellent safety in all tested species, indicating great potential for clinical application.