Fig 2: Concentration response profile of 2870(A) Average concentration-response profile of compound 2870 and known BRD4 inhibitor I-BET151 using the BRD4(1) biochemical alpha screen assay (n = 3). Emission data was normalized using DMSO and is reported as % response. Average IC50 of 2870 was found to be 9.02 µM against BRD4(1). (B) The EGFR kinase radioisotope filter binding assay was performed at a substrate concentration of 10 µM against 2870 and Staurosporine (n = 3). Average IC50 of 2870 was found to be 0.044 µM against EGFR kinase.

Fig 3: Transcriptional profiles of EGFR and BRD4 inhibitors are distinct.The box plot shows correlation matrix variances for each comparison of signatures generated by target inhibitors in the MCF7 cell line at 10 µM for 24 hours. P-values obtained by Welch’s two sample t-test comparing the populations of pairwise correlations.

Fig 4: High-throughput computational screening pipeline to identify dual inhibitors of EGFR kinase and BRD4(1).

Fig 5: ROC curves of the BRD4 docking data fusion model.The activity cutoff is (a) pIC50 = 5 and (b) pIC50 = 6. The ROC curve is true positive rate (sensitivity) over false positive rate (1 - specificity).