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Thanks for posting the link. The original article "Multicenter Preclinical Validation of BET Inhibition for the Treatment of Pulmonary Arterial Hypertension" was published on May 1, 2019. This latest "publication" from this week is a reply by the articles original authors to some other investigators who published a letter expressing concern about potential cardiotoxic effects of BET inhibitors. In the reply, the authors of the original paper state:

"In a letter, Dr Perros et al. raised concerns about the potential cardiotoxic effects of BET inhibitors in PAH patients based on published data demonstrating structural and functional alterations of the heart in healthy rodents treated with the pan-BET inhibitor I-BET-151(2). A contrast must be drawn between highly potent non-selective BET inhibitors such as I-BET-151, which are under development for oncology indications, and RVX208 which is a BD2 selective BET inhibitor with lower potency that has an excellent cardiovascular (CV) safety profile to date......To date the total exposure in high-risk CV patients is approaching 2,000 subjects with no heart failure signal identified."

This is a very important point. Almost all pre-clinical BET inhibitor data out there are for pan-BET inhibitors. Apabetalone is a bromodomain-2 selective BET inhibitor that does not elicit the same profile of transcriptional changes as a pan-BET inhibitor that non-selectively binds both BD-1 and BD-2. It is a great 1 page response. Worth a read. 

BDAZ

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