Table 1.

Properties of dual BRD4-kinase inhibitors in comparison with single activity inhibitors

BRD4-1 binding/inhibitionKinase inhibitionCell growth inhibition
CompoundΔTm,a °CIC50,b nmol/LKd,c nmol/LIC50,d nmol/LIC50,e μmol/L
IDDSFAlpha screenqPCRJAK2FLT3MM1.SUKE-1SAOS2HCC78
17.5105862.70.90.380.13
29.6274311100.160.35
311.034351.11.10.150.080.400.66
412.6146.83.4110.070.16
512.5211212320.080.160.340.79
65.126031,0001,7001.51.8
TG1012096.81300.511.51.40.321.51.9
(+)-JQ18.8219.1n.a.n.a.0.100.211.52.6
Ruxolitinib<1n.a.2.8f>100.17>10>10
Quizartinib<1n.a.1.3g>109.5>10>10
  • Abbreviation: n.a., no activity (>90% of DMSO control at 10 μmol/L concentration).

  • aMean value of 3 experiments in quadruplicate.

  • bPerformed by Reaction Biology (mean value of 2 to 3 experiments).

  • cPerformed by DiscoveRx (mean value of single experiment in duplicate).

  • dPerformed by Reaction Biology using 33P-labeled assay (single experiment).

  • eCellTiter Blue assay (mean value of 2 experiments in hexaplicate) for cell lines studied in detail.

  • fReference 50.

  • gReference 26.