Nucleotide-binding oligomerization domain-like receptors (NLRs) are intracellular sensors of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Previously, we reported nucleotide-binding oligomerization domain-containing protein 1 (NOD1) antagonists (11, 12) and a NOD2 antagonist (9) that sensitized docetaxel (DTX) or paclitaxel (PTX) treatment for breast or lung cancer. In this article, we describe for the first time a 1,4-benzodiazepine-2,5-dione (BZD) derivative (26bh) that acts as a dual NOD1/NOD2 antagonist and inhibits both nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) inflammatory signaling, thereby sensitizing PTX to suppress Lewis lung carcinoma (LLC) growth. After investigation of the compound's cytotoxicity, a systematic structure-activity relationship (SAR) was completed and revealed several key factors that were necessary to maintain antagonistic ability. This study establishes the possibility for using adjuvant treatment to combat cancer by antagonizing both NOD1 and NOD2 signaling.

A Cp*CoIII-catalyzed arene C–H bond amidation/annulation of benzamides was developed to afford quinazolinone derivatives in one-pot with high yields and broad substrate scope.

Patent and regulatory exclusivity shall constitute incentives for pharmaceutical companies to develop new drugs. This study aims to investigate the differences in the patent term extension (PTE) and regulatory exclusivity between China and the United States, and to evaluate their potential impact on the market exclusivity period of novel drugs. Small‐molecule novel drugs with their first indication approved in China and the United States between 2018 and 2021 were evaluated regarding their PTE and regulatory exclusivity. The PTE length of the China‐approved drugs was calculated by simulation, whereas that of the US‐approved drugs was extracted from the United States Patent and Trademark Office. Thirty‐two and 107 novel drugs approved in China and the United States, respectively, were included in the study. The PTE length of the US‐approved drugs calculated by the China‐PTE method was significantly longer than that calculated by the US‐PTE method. Patent extensions should be granted for 91% of new drugs in China and 82% in the United States. The simulated median PTE length of novel drugs approved in China was significantly higher than that of the United States (5.0 vs. 2.9 years, P < 0.05). It can be expected that the implementation of the PTE policy in China would significantly extend the period of market exclusivity for novel drugs similar to that of the United States. China should fully evaluate the potential impact of the PTE policy on the market exclusivity of novel drugs and provide better incentives to the development of novel drugs in addressing unmet clinical needs when developing its regulatory exclusivity policy.

A unique b-cyclodextrin (b-CD) gel with ordered structure was fabricated. The ordered aggregation of b-CD was achieved by controlling the solubility of b-CD in good/poor solvents. Physicochemical properties of the gel were systematically investigated. Mechanical properties were tested by rheological measurements, and the fibrous morphology was observed by confocal laser scanning microscopy. The anisotropic property of gel fibers was detected under polarized optical microscopy. Well-defined tetragonal and channel packed microstructures were formed in gel fibers, which revealed hollow channels of cyclodextrins. By changing physicochemical environments, macroscopic phase transitions were aroused, and self-recovering phenomena occurred when a certain amount of NaCl was added into the gel as a stimulus or the shear rate loop test was performed (thixotropy). By adjusting the concentrations of external stimuli or volume ratios of good/poor solvents, properties of the gel including mechanical strength or thermostability can be easily altered. The ordered empty channels assembled by CDs with the self-recovering properties may shed new light on this traditional host molecule.