Search, design and synthesis of new antitumor agents that inhibit bromodomains and the JAKSTAT oncogenic pathway

Cancer is a very common disease today and, according to the World Health Organization (WHO), is one of the leading causes of death worldwide. Around 14.1 million people were diagnosed with cancer in 2015. A bromodomain (BRD) is a structural module composed of approximately 110 amino acids found in various proteins involved in transcriptional activation; it is a specific protein-protein interaction domain. Members of this family include BRD2, BRD3, BRD4, and BDRT, which perform diverse functions in the regulation of transcription by RNA polymerase II. The importance of designing and searching for new molecular entities that inhibit bromodomains is correlated with the role these targets play in cell cycle control, as they play a critical role in cellular processes such as cell proliferation, apoptosis, and transcription. The STAT protein family, especially STAT1, STAT3, and STAT5, is involved in regulating cell growth, differentiation, immune response, and survival. In recent years, they have also been shown to be key in the pathogenesis of various diseases, such as cancer. Under physiological conditions, the upregulation (activation) of these transcription factors depends on stimuli from cytokines, growth factors, and estrogens, among others. They appear to be relatively dispensable in normal mature cells, while they can be essential for the survival of certain cancers. Therefore, they have become excellent molecular targets for the discovery of new molecules that can be transformed into antitumor drugs. The overall objective of this project is to identify and characterize new chemical entities that are effective in treating diseases related to bromodominoes and proteins of the JAK-STAT oncogenic pathway.

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ULL Team

• Angel Ernesto Amesty Arrieta
• Ana María Estévez Braun