Recently the results of BET-inhibitor clinical trials have highlighted the risks of on-target toxicity, especially thrombocytopenia.23,51–55 The BD2-selective RVX-208 (ref. 28) is the only BET-inhibitor to progress to phase 3, hinting at reduced toxicity.56 This low toxicity could be a result of the reduced role of BD2s in chromatin binding through three potential routes. This evidence concerns the gene DNER and Thrombocytopenia.