BRD4 Targeted Library
ChemDiv’s library of small molecules targeting BRD4 contains 5,000 compounds.
BRD4 is a critical transcriptional and epigenetic regulator essential for embryogenesis and cancer progression. As a member of the Bromodomain and Extraterminal (BET) protein family, BRD4 is distinguished by two tandem bromodomains (BD1 and BD2) that bind to acetylated lysine residues on target proteins, including histones. These domains exhibit a higher affinity for proteins with multiple acetylated residues, allowing BRD4 and other BET proteins to interact with hyper-acetylated histone regions on the chromatin. This interaction facilitates the accumulation of BRD4 at transcriptionally active regulatory elements, promoting gene transcription at both the initiation and elongation phases.
BRD4 was initially identified for its role in cell cycle regulation, associating with chromosomes during mitosis to earmark genes for rapid transcription in the G1 phase, which is necessary for cell cycle progression. The transcriptional activity of BRD4 is crucial not only during embryogenesis but also for determining cell identity. BRD4 plays a significant role in the development of diseases, particularly cancer, by acting as a key regulator of gene expression through its epigenetic and transcriptional control mechanisms. Its ability to bind to acetylated lysines on histones allows BRD4 to localize to regions of active transcription, where it can promote the expression of genes involved in cell proliferation, survival, and differentiation. In the context of cancer, BRD4 has been shown to be overexpressed in various types of tumors, where it enhances the transcription of oncogenes and other genes critical for the maintenance of the malignant phenotype. This overactivity contributes to the progression of cancer by supporting unchecked cell growth, resistance to cell death, and other hallmarks of cancer. Consequently, BRD4 is a target of interest for the development of therapeutic agents, as inhibiting its function has the potential to disrupt these pathological gene expression programs, offering a strategy to counteract tumor growth and progression.
Inhibiting BRD4 expression has been shown to hinder cancer development, positioning BRD4 as a promising target for anticancer drug development. This potential is rooted in its ability to modulate gene expression patterns that are pivotal for both normal development and the pathological progression of cancer [1]. This underscores the broader role of BRD4 in disease development, highlighting its potential as a therapeutic target in cancer and possibly other diseases where dysregulated gene expression plays a critical role.
BRD4 inhibitors represent a promising class of compounds in the field of drug discovery, offering targeted therapeutic strategies against a range of diseases, especially cancer. By selectively blocking the activity of BRD4, these inhibitors can disrupt the transcriptional programs essential for tumor cell growth and survival, leading to reduced proliferation and potentially inducing apoptosis in cancer cells. Furthermore, BRD4 inhibitors can modulate the immune response and influence the tumor microenvironment, enhancing the efficacy of existing cancer therapies and possibly overcoming resistance mechanisms. Additionally, given BRD4's involvement in various biological processes beyond oncogenesis, such as inflammation and viral replication, BRD4 inhibitors have the potential for broad therapeutic applications, making them a versatile tool in the development of new treatments for multiple diseases.
Our small molecule library of BRD4 inhibitors offers a diverse toolkit for identifying and optimizing compounds with potent anti-cancer activities, enabling the exploration of a wide range of therapeutic targets within the BRD4 pathway. The library facilitates high-throughput screening for drug discovery, accelerating the identification of candidates with favorable pharmacological profiles and the potential to address various cancers and other BRD4-related diseases efficiently.
References:
[1] B. Donati, E. Lorenzini, and A. Ciarrocchi, “BRD4 and Cancer: Going beyond transcriptional regulation,” Mol. Cancer, vol. 17, no. 1, pp. 1–13, 2018, doi: 10.1186/s12943-018-0915-9.