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Simultaneous inhibition of the bromodomain and extra-terminal domain and Aurora kinases is a promising anticancer therapeutic strategy. Based on our previous study on BET-kinase dual inhibitors, we employed the molecular docking approach to design novel dual BET-Aurora kinase A inhibitors. Through several rounds of optimization and with the guidance of the solved cocrystal structure of BRD4 bound to inhibitor 27, we finally obtained a series of highly potent dual BET-Aurora kinase A inhibitors. Compound 38exhibited strong affinity toward both BRD4 and Aurora kinase A. It also showed good antiproliferative activities on diverse cancer cell lines, good pharmacokinetic profiles, and favorable antitumor efficacy in renal cell cancer and colon cancer xenograft models with TGI of 45.99% and 53.06%, respectively. The development of compound 38reinforces the concept that a rational design may achieve dual inhibitors targeting specific kinases and bromodomain proteins.

Introducing nonvolatile liquid acids into porous solids is a promising solution to construct anhydrous proton-conducting electrolytes, but due to weak coordination or covalent bonds building these solids, they often suffer from structural instability in acidic environments. Herein, we report a series of steady conjugated microporous polymers (CMPs) linked by robust alkynyl bonds and functionalized with perfluoroalkyl groups and incorporate them with phosphoric acid. The resulting composite electrolyte exhibits high anhydrous proton conductivity at 30–120 °C (up to 4.39 × 10–3S cm–1), and the activation energy is less than 0.4 eV. The excellent proton conductivity is attributed to the hydrophobic pores that provide nanospace for continuous proton transport, and the hydrogen bonding between phosphoric acid and perfluoroalkyl chains of CMPs promotes short-distance proton hopping from one side to the other.