Resverlogix is developing apabetalone (RVX-208), a first-in-class, small molecule that is a selective BET (bromodomain
and extra-terminal) inhibitor.
The trial will evaluate the combination, safety and efficacy of the Company's ZEN-3694, a novel and differentiated bromodomain
and extra-terminal domain inhibitor, and Pfizer's talazoparib, a poly ADP ribose polymerase inhibitor, in patients with locally advanced or metastatic triple negative breast cancer without germline BRCA1/2 mutations.
Clinical response of carcinomas harboring the BRD4-NUT oncoprotein to the targeted bromodomain
According to Nuevolution, it has developed potent and selective compounds, with a benign safety profile, targeting the first bromodomain
of the BET family of proteins.
Histone acetylated lysines, under the control of the opposite action of HATs and HDACs, are recognized by bromodomain
and extra-terminal (BET) proteins.
has signed an exclusive global license agreement that provides OHM Oncology with the rights for the development, manufacture and commercialization of APL-581, as well as related molecules from Aptose's dual bromodomain
and extra-terminal domain motif (BET) protein and kinase inhibitor program.
Microarray experiments conducted on leukemia cell lines treated with the bromodomain
inhibitor JQ1 showed that JQ1 causes a significant downregulation of S100A8 and S100A9 transcripts in OCI-AML3 cells (Figure 1).
Held et al., "SMAC mimetic Debio 1143 synergizes with taxanes, topoisomerase inhibitors and bromodomain
inhibitors to impede growth of lung adenocarcinoma cells," Oncotarget, vol.
demonstrated that the inhibition of bromodomain
protein BRD4 could alleviate the expression of oncogenic lncRNA HOTAIR in GBM patients, exerting an antiproliferation effect by inducing cell cycle arrest in GBM cells [160, 161].
DNMT inhibitors (DNMTi), histone deacetylase inhibitors (HDACi), and inhibitors of the bromodomain
and extraterminal motif proteins (iBET), approved by the US Food and Drug Administration (FDA), are actually in clinical trials for several malignancies and they are reviewed in detail in .
The family of bromodomain
and extraterminal (BET) proteins is composed of four members: BRD2, BRD3, BRD4 (ubiquitously expressed), and BRDT.