Single-molecule VEGFR-2/BRD4 hybrid outperforms sorafenib plus JQ-1 in cell assays
- A pharmacophore hybridization strategy fused sorafenib's aryl urea with the tetrahydropteridinone core of BI-2536 to give dual VEGFR-2/BRD4 inhibitors.
- One lead from the analogue series showed broad antiproliferative activity and surpassed a sorafenib plus JQ-1 combination in cells.
- Kinase profiling favored VEGFR-2, and in a xenograft model the lead outperformed both single agents.
💡 Points Based on the abstract
The hybrid logic is neat, but BI-2536 is known as a PLK1 inhibitor, so a PLK1 counter-screen would show how much of the cell potency comes from VEGFR-2 and BRD4. In vivo, a matched-exposure combination arm and tumor MYC knockdown as a BRD4 engagement readout would test whether "beats the combination" holds up.