Extended Data Fig. 8: In vivo efficacy and tolerability of BD2 selective inhibitors and DbBis.
From: Selective inhibition of the BD2 bromodomain of BET proteins in prostate cancer
a, Sprague-Dawley rats (n = 3 animals per group) were treated daily with vehicle, ABBV-075 (3 mg kg−1) or ABBV-744 (30 mg kg−1) for 14 days, and platelet counts were determined using the standard method. Efficacious exposure levels of ABBV-075 (1 mg kg−1) and ABBV-744 (4.7 mg kg−1) in mice and exposure levels associated with the indicated doses of each compound in rats were determined in separate pharmacokinetic studies using different animals (n = 3 animals per group). b, Antitumour activity of well-known BET inhibitors in the xenograft model in which LNCaP cells were implanted in the mouse flank. JQ-1 and iBET-762 were administered at their respective MTD. RVX-208 was administered at its maximal achievable dose. Data are mean ± s.e.m. of tumour size for each treatment group (n = 6). WL, maximum weight loss relative to initial value; FD, found dead. c, Efficacy comparison of BET inhibitors in the LNCaP model. d, e, Mice bearing LNCaP tumours (d; n = 9 per group) or OPM2 tumours (e; n = 10 per group) were treated with vehicle or ABBV-075 using oral gavage at the indicated amounts for 21 days (PO, QDX21). Data are mean ± s.e.m. of tumour size for each treatment group.
