(+)-JQ1 is an inhibitor of bromodomain-containing protein (BRD) bromodomains.1 It inhibits bromodomain 1 (BD1) and BD2 in BRD testes-specific protein (BRDT), BRD2, BRD3, and BRD4 (IC50s = 52-217 nM in a time-resolved FRET assay). (+)-JQ1 (500 nM) reduces the levels of c-Myc, as well as induces cell cycle arrest at the G1 phase and apoptosis, in MM.1S multiple myeloma cells.2 When co-cultured with HS-5 bone marrow fibroblasts, it decreases the proliferation of RPMI-8226 B cell lymphocytes and MM.1S, KMS-20, L-363, and AMO1 multiple myeloma cells when used at a concentration of 1 µM. (+)-JQ1 (50 mg/kg per day) decreases tumor burden and increases survival in an MM.1S orthotopic mouse model. It also reduces testis weight, testis tubule area, sperm count, sperm motility, and the number of pups per litter without reducing the levels of testosterone, luteinizing hormone, or follicle-stimulating hormone (FSH) in male mice when administered at a dose of 50 mg/kg per day.3 See the Structural Genomics Consortium (SGC) website for more information.

1.1: morpholine; sulfur / ethanol / 12 h / 23 - 70 °C
2.1: N-ethyl-N,N-diisopropylamine; HCTU / N,N-dimethyl-formamide / 16 h / 23 °C
3.1: piperidine / N,N-dimethyl-formamide / 0.5 h / 23 °C
4.1: silica gel / ethanol / 3 h / 90 °C
5.1: potassium tert-butylate / tetrahydrofuran / 0.5 h / -78 - 23 °C
5.2: 0.75 h / -10 °C
5.3: 2 h / 23 - 90 °C

1.Current Patent Assignee: DANA FARBER CANCER INSTITUTE - WO2011/143657, 2011, A1
2.Liu, Z., Tian, B., Chen, H., et al. Discovery of potent and selective BRD4 inhibitors capable of blocking TLR3-induced acute airway inflammation. Eur. J. Med. Chem. 151, 450-461 (2018).

3.Delmore, J.E., Issa, G.C., Lemieux, M.E., et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell 146(6), 904-917 (2011).

4.Matzuk, M.M., McKeown, M.R., Filippakopoulos, P., et al. Small-molecule inhibition of BRDT for male contraception. Cell 150, 673-684 (2012).