Multitargeting HDAC Inhibitors Containing a RAS/RAF Protein Interfering Unit.

In this work, a series of multitargeting histone deacetylase (HDAC) inhibitors capable of regulating the signal transduction between RAS protein and downstream effectors were obtained by introducing a zinc-ion-binding group into the framework of rigosertib via different linkers. Among them, two representative compounds, and , not only showed stronger antiproliferative activity against many types of cancer cells including solid tumor cells but also presented more potent inhibition on different subtypes of HDAC than suberoylanilide hydroxamic acid (SAHA). Significantly, presented moderate pharmacokinetic behaviors and showed stronger antitumor activity than oxaliplatin, SAHA, and rigosertib in the HT-29 xenograft mouse models without significant systemic toxicity.

Design, synthesis and biological evaluation of cinnamamide-quinazoline derivatives as potential EGFR inhibitors to reverse T790M mutation.

Gatekeeper T790M mutation in EGFR is the most common factor for acquired resistance. Acrylamide-bearing 4-anilinoquinazoline scaffold are powerful irreversible inhibitors for overcoming resistance. In this work, three series of EGFR inhibitors derived from incorporation of cinnamamide into the quinazoline scaffold were designed and synthesized to reverse resistance resulting from insurgence of T790M mutation.

Design, synthesis and biological evaluation of sulfamoylphenyl-quinazoline derivatives as potential EGFR/CAIX dual inhibitors.

Multi-target, especially dual-target, drug design has become a popular research field for cancer treatment. Development of small molecule dual-target inhibitors through hybridization strategy can provide highly potent and selective anticancer agents. In this study, three series of quinazoline derivatives bearing a benzene-sulfonamide moiety were designed and synthesized as dual EGFR/CAIX inhibitors.

One-for-all intelligent core-shell nanoparticles for tumor-specific photothermal-chemodynamic synergistic therapy.

Reasonable management of the one-for-all nanoplatform can facilitate improved cancer therapy. Here, the metal-organic frameworks (MOFs) based on iron(iii) carboxylate material (MIL-101-NH) were in situ decorated on stabilized polydopamine nanoparticles (PDANPs), which subsequently loaded glucose oxidase (GOx) via hyaluronic acid (HA) coating to structure the one-for-all intelligent core-shell nanoparticles (HG-MIL@PDANPs). Because of the inner PDANPs, the HG-MIL@PDANPs could realize near-infrared (NIR)-controllable site-specific photothermal therapy (PTT).

ROS-responsive and multifunctional anti-Alzheimer prodrugs: Tacrine-ibuprofen hybrids via a phenyl boronate linker.

Current drugs available in clinic for Alzheimer's disease (AD) treatment can only alleviate disease symptoms without clearly curing or delaying the process of AD. And some AD drugs failed in Phase III clinical trials are only focused on targeting amyloid-β (Aβ). Therefore, an alternative strategy in AD drug design is meaningful to be involved in the multiple pathogenic factors which can affect each other at multiple levels.