BET（bromodomain and extraterminal domain) is a protein family composed of four members: BRD2, BRD3, BRD4 and BRDT. BET plays a key role in tumorigenesis by controlling the expression of oncogenes such as c-Myc. BET proteins can specifically recognize lysine acetylated histones, thereby regulating gene transcription for a wide variety of cellular functions. Cell cycle, cell differentiation, signal transduction and other processes can be affected through modification non-histone proteins such as, acetylation of transcription factors. An increased activity of BET in tumor cells can lead to high expression of the oncogenic protein MYC that in turn, promotes tumor growth. MYC, as an oncogenic transcription factor, has historically been difficult to directly target due to its unfolded protein structure. JAB-8263 is a very potent inhibitor with a subnanomolar binding affinity to BET. JAB-8263 inhibits MYC expression by inhibiting the activity of BET, an upstream regulator of MYC transcription; lower levels of MYC consequently inhibit tumor growth.

 

Clinical studies with JAB-8263 have shown anti-tumor activities in a variety of advanced solid tumor types, including NUT midline cancer, non-small cell lung cancer, small cell lung cancer, castration resistant prostate cancer, ovarian cancer, and colorectal cancer. Anti-tumor activities have also been observed in preliminary studies of BET inhibitors in hematological tumors, including relapsed/refractory (R/R) lymphoma, acute myeloid leukemia, and myelofibrosis.