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Drug resistance caused by epidermal growth factor receptor (EGFR) mutation has largely limited the clinical use of EGFR tyrosine kinase inhibitors (EGFR-TKIs) for the treatment of non-small-cell lung cancer (NSCLC). Herein, to overcome the intractable problem of drug resistance, proteolysis targeting chimeras (PROTACs) targeting EGFR mutants were developed by optimizing covalent EGFR ligands. Covalent or reversible covalent pyrimidine- or purine-containing PROTACs were designed, synthesized, and evaluated. As a consequence, covalent PROTAC CP17 , with a novel purine-containing EGFR ligand, was discovered as a highly potent degrader against EGFR L858R/T790M and EGFR del19 , reaching the lowest DC 50 values among all reported EGFR-targeting PROTACs. Furthermore, CP17 exhibited excellent cellular activity against the H1975 and HCC827 cell lines with high selectivity. Mechanism investigation indicated that the lysosome was involved in the degradation process. Importantly, the covalent binding strategy was proven to be an effective approach for the design of PROTACs targeting EGFR L858R/T790M , which laid the practical foundation for further development of potent EGFR-targeting PROTACs.

Mixed lineage leukemia (MLL) gene rearrangements are associated with acute leukemia. The protein menin is regarded as a critical oncogenic cofactor of the resulting MLL fusion proteins in acute leukemia. A direct interaction between menin and the MLL amino terminal sequences is necessary for MLL fusion protein-mediated leukemogenesis. Thus, inhibition of the interaction between menin and MLL has emerged as a novel therapeutic strategy. Recent improvements in structural biology and chemical reactivity have promoted the design and development of selective and potent menin-MLL interaction inhibitors. In this Perspective, different classes of menin-MLL interaction inhibitors are comprehensively summarized. Further research potential, challenges, and opportunities in the field are also discussed.

A practically useful approach for the cross-dehydrogenative coupling of quinazolin-4-one with simple nonactivated alkanes is reported. The products were smoothly formed under mild reaction conditions, within short reaction time at ambient temperature. The formation of new Csp 3 -Csp 2 bonds occurred at the electron-poor C-2 position of quinazolin-4-one. The approach has the potential to be an important tool for the late-stage functionalization of advanced synthetic intermediates and may find many applications in medicinal chemistry.

BF 3 ·OEt 2 -mediated cross-coupling of (SnMe 3 ) 2 with aryl triazene offers a new strategy for the synthesis of aryl stannane. A variety of synthetically useful aryl trimethylstannanes were produced in moderate to good yields with this metal-free approach. One-pot sequential Stille cross-coupling with different aryl bromides provides a short entry to both symmetrical and unsymmetrical biaryl compounds.

Convenient silylborane precursors for introducing N,B-bidentate boryl ligands onto transition metals were designed, prepared, and employed in ready formation of irdium(III) complexes via Si-B oxidative addition. A practical, efficient catalytic ortho-borylation reaction of arenes with a broad range of directing groups was developed using an in situ generated catalyst from the silylborane preligand 3c and [IrCl(COD)] 2 .

A new chemistry of hydrazines that is a copper-catalyzed radical reaction to synthesize vinyl sulfones from readily available N-tosylhydrazones has been described. The protocol provides a novel strategy for the synthesis of various vinyl sulfones including α, β-disubstituted ones and terminal ones. The advantages of the transformation include excellent E stereoselectivity, broad substrate scope, low cost of reagents, and convenient operation. A novel and efficient one-pot synthesis of alkynes from N-tosylhydrazones has been achieved. The studies provide important complementary approaches for the syntheses of vinyl sulfones and alkynes.

A general and efficient palladium-catalyzed intermolecular direct C-H homocoupling of furans and thiophenes has been developed. The reaction is characterized by using molecular oxygen as the sole oxidant and complete C5-position regioselectivity. Both C2- and C3-substituted furans or thiophenes are appropriate substrates. The approach provides a straightforward, facile, and economical route to bifurans and bithiophenes under mild reaction conditions.

An efficient and economical palladium-catalyzed oxidation system has been identified. The oxidation system, characterized by not adding ligand and using molecular oxygen as the sole oxidant, can realize the Tsuji-Wacker oxidation of terminal olefins and especially styrenes to methyl ketones; in addition, this system can achieve tandem Wacker oxidation-dehydrogenation of terminal olefins to α,β-unsaturated ketones.

In this study, a kind of unique Fe2O3/Pt hybrid consisting of uniform platinum nanoparticles deposited on a nanoflake-shaped Fe2O3 support was prepared by using a solvothermal reaction followed by a heat-induced reduction process. The prepared Fe2O3 sample displays well-defined nanoflake-like morphology; remarkably, there are many specific cavities on its surface. In addition, uniform Pt nanoparticles with narrow size distribution were deposited onto the surface of the preformed flake-like Fe2O3 support to form the Fe2O3/Pt hybrid via a facile heat-induced reduction reaction. Thus, the prepared Fe2O3/Pt hybrid can serve as heterogeneous catalyst over the hydrogenation reaction. Results demonstrated that the specific Fe2O3/Pt heterogeneous catalyst exhibits good catalytic performances, including high conversion, specific selectivity, and excellent recycling durability, over hydrogenation reactions for different substrates. Furthermore, the prepared Fe2O3/Pt heterogeneous catalyst could be easily separated from the product mixture by using a magnet and could be recycled for 10 cycles without catalytic activity loss. In a word, the present synthetic approach is facile, scalable, and reproducible, which can be easily facilitated to prepare other types of noble metals/metal oxide composite systems.