Reshaping acetylated peptide selectivity between human BET Brd2 bromodomains BD-I and BD-II in glioblastoma by rationally grafting secondary anchor residues.
OTX015 displayed higher antiproliferative effects compared to its analog JQ1, with GI50 values of approximately 0.2 µM. In addition, C-MYC and CDKN1A mRNA levels increased transiently after 4 h-exposure to OTX015, while BRD2, SESN3, HEXIM-1, HIST2H2BE, and HIST1H2BK were rapidly upregulated and sustained after 24 h. Studies in three additional GBM cell lines supported the antiproliferative effects of OTX015.
We demonstrate that BRD2 and BRD4 RNA are significantly overexpressed in GBM, suggesting that BET protein inhibition may be an effective means of reducing GBM cell proliferation.
To determine the feasibility of MIBG targeting for a wider range of tumor types, we employed plasmid-mediated transfer of the NAT gene into a human glioblastoma cell line (UVW) which does not express the NAT gene.