Discovery and evaluation of HW161023 as a potent and orally active AAK1 inhibitor.

AAK1, also known as AP2-associated protein kinase 1, is an enzyme that belongs to the family of serine/threonine protein kinases. It regulates the assembly and disassembly of clathrin-coated pits and thereby protein endocytosis, by phosphorylating the μ2 subunit of the AP2 complex, which is a key component of clathrin-coated vesicles. LX9211 is currently the only selective small molecule AAK1 inhibitor at the clinical trial stage for diabetic peripheral neuropathic pain, which was found to be safe and well tolerated in healthy participants in phase I clinical trials.

Multifunctional BiS-Au nanoclusters for fluorescence/infrared thermal imaging guided photothermal therapy.

Nanotechnology has attracted extensive attention in the diagnosis and treatment of cancer. Therefore, the research aimed at developing new nanomaterials and exploring their applications in biomedicine has attracted more attention. In this study, BiS-Au nanoclusters (BiS-AuNCs) as fluorescence/infrared thermal imaging-guided photothermal therapy (PTT) was prepared for the first time.

Discovery of Potent and Oral Bioavailable MAT2A Inhibitors for the Treatment of MTAP-Deleted Tumors.

Inhibition of methionine adenosyltransferase 2A (MAT2A) has received significant interest because of its implication as a synthetic lethal target in methylthioadenosine phosphorylase (MTAP)-deleted cancers. Here, we report the discovery of a series of 3-pyrido[1,2-]pyrimidin-3-one derivatives as novel MAT2A inhibitors. The selected compound exhibited high potency for MAT2A inhibition and a favorable pharmacokinetic profile.

Discovery and Evaluation of Pyrazolo[3,4-]pyridazinone as a Potent and Orally Active Irreversible BTK Inhibitor.

The identification and lead optimization of a series of pyrazolo[3,4-]pyridazinone derivatives are described as a novel class of potent irreversible BTK inhibitors, resulting in the discovery of compound . Compound exhibited high potency against BTK kinase and acceptable PK profile. Furthermore, compound demonstrated significant in vivo efficacy in a mouse-collagen-induced arthritis (CIA) model.

Long non-coding RNA FOXD2-AS1 aggravates nasopharyngeal carcinoma carcinogenesis by modulating miR-363-5p/S100A1 pathway.

Long non-coding RNAs (lncRNAs) have been wildly verified to modulate multiple tumorigenesis, especially nasopharyngeal carcinoma (NPC). In present study, we aim to investigate the role of lncRNA FOXD2-AS1 in the NPC carcinogenesis. It was indicated that FOXD2-AS1 was markedly increased in NPC tissues and cells in comparison to their corresponding controls.

Bufexamac ameliorates LPS-induced acute lung injury in mice by targeting LTA4H.

Neutrophils play an important role in the occurrence and development of acute lung injury (ALI). Leukotriene B4 (LTB4), a hydrolysis product of epoxide leukotriene A4 (LTA4) catalyzed by LTA4 hydrolase (LTA4H), is one of the most potent chemoattractants for neutrophil. Bufexamac is a drug widely used as an anti-inflammatory agent on the skin, however, the mechanism of action is still not fully understood.

Discovery of Potent Benzofuran-Derived Diapophytoene Desaturase (CrtN) Inhibitors with Enhanced Oral Bioavailability for the Treatment of Methicillin-Resistant Staphylococcus aureus (MRSA) Infections.

Blocking the staphyloxanthin biosynthesis process has emerged as a new promising antivirulence strategy. Previously, we first revealed that CrtN is a druggable target against infections caused by pigmented Staphylococcus aureus (S. aureus) and that naftifine was an effective CrtN inhibitor.