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Significance In this work, we describe a dual-action inhibitor that simultaneously disrupts functions of two key MYC-mediating factors—PI3K and BRD4. We show that the concomitant inhibition of PI3K and BRD4 blocksMYC expression and activation, promotes MYC degradation, and markedly inhibits cancer cell growth and metastasis. Our findings suggest that the dual-activity inhibitor represents a highly promising lead compound for the development of novel anticancer therapeutics.

Dual-activity PI3K–BRD4 inhibitor for the orthogonal inhibition of MYC to block tumor growth and metastasis