Last update 01 Nov 2024

BRPF1 x BRPF2

Last update 01 Nov 2024

Basic Info

Related Targets

BRPF1BRPF2

Drugs associated with BRPF1 x BRPF2

NI-57

Target

BRPF1 x BRPF2

Mechanism

BRPF1 inhibitors [+1]

Active Org.

University College London

Originator Org.

University College London

Active Indication

Inflammation

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with BRPF1 x BRPF2

100 Translational Medicine associated with BRPF1 x BRPF2

0 Patents (Medical) associated with BRPF1 x BRPF2

Literatures (Medical) associated with BRPF1 x BRPF2

01 Jan 2024·Journal of Biological Chemistry

Uncovering the non-histone interactome of the BRPF1 bromodomain using site-specific azide-acetyllysine photochemistry

Article

Author: Sudhamalla, Babu ; Barman, Soumen ; Padhan, Jyotirmayee

Bromodomain-PHD finger protein 1 (BRPF1) belongs to the BRPF family of bromodomain-containing proteins. Bromodomains are exclusive reader modules that recognize and bind acetylated histones and non-histone transcription factors to regulate gene expression. The biological functions of acetylated histone recognition by BRPF1 bromodomain are well characterized; however, the function of BRPF1 regulation via non-histone acetylation is still unexplored. Therefore, identifying the non-histone interactome of BRPF1 is pivotal in deciphering its role in diverse cellular processes, including its misregulation in diseases like cancer. Herein, we identified the non-histone interacting partners of BRPF1 utilizing a protein engineering-based approach. We site-specifically introduced the unnatural photo-cross-linkable amino acid 4-azido-L-phenylalanine into the bromodomain of BRPF1 without altering its ability to recognize acetylated histone proteins. Upon photoirradiation, the engineered BRPF1 generates a reactive nitrene species, cross-linking interacting partners with spatio-temporal precision. We demonstrated the robust cross-linking efficiency of the engineered variant with reported histone ligands of BRPF1 and further used the variant reader to cross-link its interactome. We also characterized novel interacting partners by proteomics, suggesting roles for BRPF1 in diverse cellular processes. BRPF1 interaction with interleukin enhancer-binding factor 3, one of these novel interacting partners, was further validated by isothermal titration calorimetry and co-IP. Lastly, we used publicly available ChIP-seq and RNA-seq datasets to understand the colocalization of BRPF1 and interleukin enhancer-binding factor 3 in regulating gene expression in the context of hepatocellular carcinoma. Together, these results will be crucial for full understanding of the roles of BRPF1 in transcriptional regulation and in the design of small-molecule inhibitors for cancer treatment.

01 Jan 2024·Journal of Molecular Graphics and Modelling

Integrated virtual screening and MD simulation approaches toward discovering potential inhibitors for targeting BRPF1 bromodomain in hepatocellular carcinoma

Article

Author: Sudhamalla, Babu ; Padhan, Jyotirmayee ; Barman, Soumen ; Bardhan, Ishita

Hepatocellular carcinoma (HCC) is one of the most aggressive and life-threatening cancers. Although multiple treatment options are available, the prognosis of HCC patients is poor due to metastasis and drug resistance. Hence, discovering novel targets is essential for better therapeutic development for HCC. In this study, we used the cancer genome atlas (TCGA) dataset to analyze the expression of bromodomain-containing proteins in HCC, as bromodomains are emerging attractive therapeutic targets. Our analysis identified BRPF1 as the most highly upregulated gene in HCC among the 43 bromodomain-containing genes. Upregulation of BRPF1 was significantly associated with poorer patient survival. Therefore, targeting BRPF1 may be an approach for HCC treatment. Previously, several potential inhibitors of BRPF1 bromodomain have been discovered. However, due to the limited clinical success of the current inhibitors, we aim to search for new inhibitors with high affinity and specificity for the BRPF1 bromodomain. In this study, we utilized high-throughput virtual screening methods to screen synthetic and natural compound databases against the BRPF1 bromodomain. In addition, we used machine learning-based QSAR modeling to predict the IC50 values of the selected BRPF1 bromodomain inhibitors. Extensive MD simulations were used to calculate the binding free energies of BRPF1 bromodomain and inhibitor complexes. Using this approach, we identified four lead scaffolds with a similar or better binding affinity towards the BRPF1 bromodomain than the previously reported inhibitors. Overall, this study discovered some promising compounds that have the potential to act as potent BRPF1 bromodomain inhibitors.

11 Jun 2020·Journal of Molecular Cell BiologyQ2 · BIOLOGY

Isoform-specific involvement of Brpf1 in expansion of adult hematopoietic stem and progenitor cells

Q2 · BIOLOGY

ArticleOA

Author: He, Jincan ; Zhao, Meng ; Hong, Mengzhi ; He, Qiuping ; Zhao, Wei ; Chen, Weixin

AbstractBromodomain-containing proteins are known readers of histone acetylation that regulate chromatin structure and transcription. Although the functions of bromodomain-containing proteins in development, homeostasis, and disease states have been well studied, their role in self-renewal of hematopoietic stem and progenitor cells (HSPCs) remains poorly understood. Here, we performed a chemical screen using nine bromodomain inhibitors and found that the bromodomain and PHD finger-containing protein 1 (Brpf1) inhibitor OF-1 enhanced the expansion of Lin−Sca-1+c-Kit+ HSPCs ex vivo without skewing their lineage differentiation potential. Importantly, our results also revealed distinct functions of Brpf1 isoforms in HSPCs. Brpf1b promoted the expansion of HSPCs. By contrast, Brpf1a is the most abundant isoform in adult HSPCs but enhanced HSPC quiescence and decreased the HSPC expansion. Furthermore, inhibition of Brpf1a by OF-1 promoted histone acetylation and chromatin accessibility leading to increased expression of self-renewal-related genes (e.g. Mn1). The phenotypes produced by OF-1 treatment can be rescued by suppression of Mn1 in HSPCs. Our findings demonstrate that this novel bromodomain inhibitor OF-1 can promote the clinical application of HSPCs in transplantation.

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