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Pelabresib
Pelabresib (CPI-0610; PELA) is an investigational oral small-molecule drug designed to inhibit bromodomain and extra-terminal domain (BET)-mediated gene transcription involved in the pathogenesis of myelofibrosis (MF) and other myeloproliferative neoplasms. Developed by Constellation Pharmaceuticals, a Novartis company, pelabresib targets epigenetic pathways to modulate oncogenic and inflammatory gene expression, offering a novel therapeutic approach for MF patients with limited treatment options. As of May 2025, pelabresib is in Phase III clinical trials for MF and has shown promising results in combination with ruxolitinib, a Janus kinase inhibitor (JAKi), but is not yet approved for clinical use. Mechanism of Action Pelabresib is a selective inhibitor of BET proteins (BRD2, BRD3, BRD4, BRDT), which regulate gene expression by binding to acetylated histones. In MF, BET proteins drive the expression of genes involved in nuclear factor kappa B (NF-κB) signaling, proinflammator ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Bromodomain And Extra-terminal Domain
A bromodomain is an approximately 110 amino acid protein domain that recognizes acetylated lysine residues, such as those on the ''N''-terminal tails of histones. Bromodomains, as the "readers" of lysine acetylation, are responsible in transducing the signal carried by acetylated lysine residues and translating it into various normal or abnormal phenotypes. Their affinity is higher for regions where multiple acetylation sites exist in proximity. This recognition is often a prerequisite for protein-histone association and chromatin remodeling. The domain itself adopts an all-α protein fold, a bundle of four alpha helix, alpha helices each separated by loop regions of variable lengths that form a hydrophobic pocket that recognizes the acetyl lysine. Discovery The bromodomain was identified as a novel structural motif by John W. Tamkun and colleagues studying the Drosophila gene ''Brahma (protein), Brahma''/''brm'', and showed sequence similarity to genes involved in transcriptiona ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |