"Do you have evidence to show that apabetalone has a beneficial effect through a modulation on EndMT?"

In this article, the authors document the role of the ATP-binding cassette transporter (ABCA1), a regulator of cholesterol transport in the progression of colorectal cancer. ABCA1 is significantly overexpressed in patients at advanced stages of colorectal cancer, and when cells over-expressing ABCA1 were treated with RVX-208 (in vitro) ABCA1 protein levels decreased to levels comparable to those in control cells.  They also demonstrated that RVX-208 could revert the EMT phenotype present in cells overexpressing the ABCA1.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1002/1878-0261.12367

Bromodomain proteins are known to be involved in EMT and fibrosis  and BET inhibition (in general, not necessarily with apabetalone) is known to counteract pathological EMT processes, in part through downregulation of NF-kB and IFNγ, two well-studied  proinflammatory transcription factors.  For example, here are highlights from this recent article entitled Bromodomain-containing protein 4 contributes to renal fibrosis through the induction of epithelial-mesenchymal transition:

·       Brd4 was upregulated in renal tissues of hypertensive nephropathy patients.

·       The Brd4 inhibitor attenuates Ang II-induced renal injury both in vivo and in vitro.

·        The suppression of EMT is an underlying mechanism of Brd4 inhibitor therapy in renal fibrosis.

 https://www.sciencedirect.com/science/article/abs/pii/S0014482719303490

The excellent review article that Bear linked this morning provides more information on the role of BETs in promoting EMT and fibrosis in various tissues, and the capacity of BETis to reverse the EMT process.

https://www.frontiersin.org/articles/10.3389/fphar.2019.01315/full

Jupe