Arv 825

TNBC and ovarian cell lines, MDA-MB-231 and BT549 and SKOV3, respectively, were cultured in DMEM, and ovarian cells OVCAR3 were cultured in RPMI supplemented with inactivated fetal bovine serum (10%), antibiotics (100 U/mL penicillin and 100 /mL streptomycin) and L-glutamine (2 mM) (Gibco (Thermofisher), Sigma-Aldrich) (37 °C, 5% CO₂). All cell lines used were provided by Drs. J. Losada and A. Balmain, who purchased them from the ATCC, in 2015. Cells authenticity was confirmed by STR analysis at the molecular biology unit at the Salamanca University Hospital. MDA-MB-231-derived resistant cell line (MDA-MB-231R) was obtained by pulsed exposure to increasing doses of JQ1 (72 h pulses every 2 weeks for 6 months).
BET inhibitors (JQ1 (HPLC: 99.6% purity) and OTX-015 (HPLC: 99.82% purity) and PROTACs-BRD4 (MZ1 (HPLC: 99.5% purity) and ARV-825 (LCMS: 99.37% purity)), together with the inactive form of MZ1, cis-MZ1 (HPLC: 98.6% purity), were purchase from Selleckchem (Houston, TX) and Tocris Bioscience (Bio-Techne R&D Systems, S.LU).

Apabetalone (RVX-208; BET inhibitor, S7295), ARV-825 (BRD4 specific inhibitor, S8297), AZD-5153 6-hydroxy-2-naphthoic acid (BET/BRD4 inhibitor, S8344), CPI-203 (BET inhibitor, S7304), Molibresib (I-BET-762; BET inhibitor, S7189), (+)-JQ1 (BET inhibitor, S7110), INCB054329 (BET inhibitor, S8753), MS436 (BET inhibitor, S7305), Birabresib (OTX015; BET inhibitor, S7360), PLX51107 (a new BET inhibitor, S8739), and PFI-1 (PF-6405761; BRD2/BRD4 inhibitor, S1216) were purchased from Selleck.cn, and ZL0580 (a BRD4-specific inhibitor) was prepared as previously described (20 (link), 45 (link)). The structures and functions of these inhibitors are shown in Fig. 3A, Text S1 in the supplemental material (see also Selleck.cn [https://www.selleck.cn]), and Table 1 (20 (link), 41 (link), 46 (link)– (link)55 (link)).

(+)-JQ-1 (Cat no. SML1524-5MG) was purchased from Sigma. ABBV-075 (Cat no. S8400) (ClinicalTrails.gov Identifier: NCT02391480), OTX015 (Cat no. S7360) (ClinicalTrails.gov Identifier: OTX015&draw=2&rank=5">NCT02698176), ARV-825 (Cat no. S8297) and ML385 (Cat no. S8790) were purchased from Selleckchem. Dimethyl sulfoxide (DMSO) (Item no. 10127403) was purchased from Thermo Fisher Scientific. 4-octyl itaconate (4-OI) was purchased from MedChemExpress (Cat. no. HY-112675). Dimethyl fumarate (DMF) was purchased from Sigma (Cat. No. 227056). Ruxolitinib was purchased from InvivoGen (Cat. No. tlrl-rux). IFN-α2a (Roferon) was obtained from Roche.