Discovery of 7-azaindole-3-acrylamide inhibitors of inflammasomes/IL-1β for the treatment of inflammatory bowel disease.

Currently, a significant proportion of patients with inflammatory bowel disease (IBD) fail to respond to conventional drug therapies such as immunosuppressants and biologic agents. IL-1 signaling blockade is a promising therapeutic strategy for these unresponsive IBD patients. In this study, we identified a novel anti-NLRP3/ IL-1β inhibitor, the 7-azaindole analogue Y19, which exhibits an IC value of 1.

Discovery of novel 8-hydroxyquinoline derivatives as NLRP3 inflammasome inhibitors with therapeutic potential for inflammatory bowel disease.

The activation of the NLRP3 inflammasome occurs through two distinct phases-priming and activation-and plays a significant role in various diseases including inflammatory conditions, cancer, and autoimmune disorders. Recent studies have highlighted its critical involvement in the development and progression of inflammatory bowel disease (IBD). In this study, we identified a novel 8-hydroxyquinoline derivative, compound 10, as a potent inhibitor of NLRP3 inflammasome activation.

Discovery, synthesis, and biological mechanism evaluation of novel quinoline derivatives as potent NLRP3 inhibitors.

Targeting NLRP3 is a highly promising strategy for treating uncontrolled inflammation, which can cause a wide range of diseases or promote disease progression. More NLRP3-targeting inhibitors with different scaffolds are needed to increase the chances of developing safe and effective NLRP3 inhibitors and treating inflammation in different tissues. Here, we discovered the novel quinoline analogues that exhibit potent inhibitory activity against the NLRP3/IL-1β pathway in J774A.

Artemisitene shows superiority over artemisinin in preventing Schistosoma japonica-induced liver disease.

Background: Artemisinin (ART) analogs, such as dihydroartemisinin, arteether, artemether, and artesunate, all featuring an endoperoxide bridge, have demonstrated efficacy against schistosomiasis. Artemisitene (ATT), which contains an additional α, β-unsaturated carbonyl structure, has shown enhanced biological activities. This study aims to evaluate the anti-schistosomaiasis japonica activity of ATT and compare it with ART.

Design, synthesis and biological evaluation of tanshinone IIA derivatives as NLRP3 inflammasome inhibitors.

Natural product structures have long provided valuable pharmacophores and even candidates for drug discovery. Tanshinone scaffold showed moderately inhibitory activity in NLRP3 inflammasome/IL-1β pathway. Herein, we designed a series of derivatives on different regions of Tanshinone IIA (TNA) scaffold.

Discovery of a dual-acting inhibitor of interleukin-1β and STATs for the treatment of inflammatory bowel disease.

Currently, a significant proportion of inflammatory bowel disease (IBD) patients fail to respond to conventional drug therapy such as immunosuppressants and biologic agents. Interference with the JAK/STAT pathway and blocking of IL-1 signaling are two promising therapeutic strategies for these unresponsive IBD patients. This work describes the discovery of an inhibitor 10v that not only blocks NLRP3 and AIM-2 inflammasome-mediated IL-1β signaling, but also reduces the expression of STAT1 and STAT5 in the JAK/STAT pathway.

Discovery of a selective NLRP3-targeting compound with therapeutic activity in MSU-induced peritonitis and DSS-induced acute intestinal inflammation.

The aberrant activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is known to contribute to the pathogenesis of various human inflammation-related diseases. However, to date, no small-molecule NLRP3 inhibitor has been used in clinical settings. In this study, we have identified SB-222200 as a novel direct NLRP3 inhibitor through the use of drug affinity responsive target stability assay, cellular thermal shift assay, and surface plasmon resonance analysis.

Artemisinin-derived artemisitene blocks ROS-mediated NLRP3 inflammasome and alleviates ulcerative colitis.

Artemisinins are well-known antimalarial drugs with clinical safety. In addition to antimalarial effects, their anti-inflammatory and immunoregulatory properties have recently attracted much attention in the treatment of inflammatory diseases. However, these artemisinins only have sub-millimolar anti-inflammatory activity in vitro, which may pose a high risk of toxicity in vivo with high doses of artemisinins.

Synthesis of highly functionalized 2,4-diaminoquinazolines as anticancer and anti-HIV agents.

Novel polyhalo 2,4-diaminoquinazolines 3a-3d were prepared by reacting polyhaloisophthalonitriles with guanidine carbonate under solvent-free conditions and in the absence of a catalyst with good yields (74-95%). A series of highly functionalized 2,4-diaminoquinazolines 4-5 were then synthesized based on 3a-3c. The anticancer activities of compounds 3-5 were evaluated in vitro against human cell lines such as Skov-3, HL-60, A431, A549, and HepG-2.

1-(2,6-Difluoro-benzo-yl)-3-(2,3,5-tri-chloro-phen-yl)urea.

The asymmetric unit of the title compound, C(14)H(7)Cl(3)F(2)N(2)O(2), contains two unique molecules. The 2,3,5-trichloro-phenyl ring is almost coplanar with the urea group in both molecules, whereas the 2,6-difluoro-phenyl ring is twisted from the urea plane by 54.83 (10)° in one molecule and 60.