Xiao-Long Wang’s research while affiliated with Xi'an Technological University and other places

The abnormal overexpression of FLT3 kinase is intimately associated with pathogenesis of acute myeloid leukemia (AML), positioning FLT3 inhibitors as pivotal therapeutic agents. Despite the availability of three FDA‐approved FLT3 inhibitors, their clinical utility is hampered by resistance stemming from tyrosine kinase domain (TKD) mutations. Through an integrative analysis of case studies, we identified a potential advantage of type I FLT3 inhibitors in overcoming TKD mutation‐induced resistance. Structure–activity relationships (SAR) analysis indicated that FW‐1 exhibited over 50% inhibition against FLT3 at a concentration of 1 μM and demonstrated potent activity against AML cell lines MV4‐11 (IC 50 = 2.68 μM) and MOLM‐13 (IC 50 = 1.03 μM). In our cellular mechanistic studies, FW‐1 also effectively induced apoptosis by arresting cell cycle progression in the G0/G1 phase. This study introduces FW‐1 as a promising lead for type I FLT3 inhibitor, warranting further optimization.

This study examines the low‐loss and temperature‐stable Na2O–Ln2O3–MoO3–TiO2 (Ln = Nd, La and Ce) system, synthesized via a solid‐state process at low‐sintering temperatures ranging from 840°C to 900°C The structure, microstructure and microwave properties of the Na0.5Ln0.5MoO4–TiO2 (Ln = Nd, La and Ce) ceramics as a function of the sintering temperature were studied. The results of XRD patterns and microstructure characterization showed that the main phase in compositions belong to tetragonal scheelite and tetragonal structure. The ceramic composition Na0.5Ln0.5MoO4–TiO2 (Ln = Nd, La and Ce), sintered at 840°C–900°C for 2 hours, demonstrated excellent microwave dielectric properties, exhibiting relative dielectric constant (εr) of 13.9–14.4, Q × f value of about 31 100 (at 9.66 GHz) – 48 600 GHz (at 9.33 GHz), and temperature coefficient of –8.1 to –1 ppm/°C. Our work designs temperature‐stable microwave dielectric ceramics with low‐sintering temperature for LTCC technology applications.

Sodium–sulfur (Na–S) batteries are considered as a promising successor to the next-generation of high-capacity, low-cost and environmentally friendly sulfur-based battery systems. However, Na–S batteries still suffer from the “shuttle effect” and sluggish ion transport kinetics due to the dissolution of sodium polysulfides and poor conductivity of sulfur. MXenes, as 2D transition metal carbides/nitrides, have exhibited excellent conductivity, diverse structure and tunable surface groups, particularly playing a crucial role in inhibiting polysulfide shuttle and sodium dendrite growth. In this review, achievements and advancements of MXene-based Na–S batteries are discussed, including applications of a sulfur cathode, separator, interlayer between separator and cathode, and sodium anode. In the end, perspectives and challenges on the future development of MXene-based materials in Na–S batteries are proposed.

The FLT3-ITD (internal tandem duplication) mutant has been a promising target for acute myeloid leukemia (AML) drug discovery, but is now facing the challenge of resistance due to point mutations. In this study, we have discovered a new type II FLT3 kinase inhibitor, SILA-123. This inhibitor has shown highly potent inhibitory effects against FLT3-WT (IC50 = 2.1 nM) and FLT3-ITD (IC50 = 24.9 nM), tumour cells with FLT3-ITD mutant such as MOLM-13 (IC50 = 0.98 nM) and MV4-11 (IC50 = 0.19 nM), as well as BaF3 cells associated with FLT3-ITD mutant and point mutations including BaF3-FLT3-ITD-G697R (IC50 = 3.0 nM), BaF3-FLT3-ITD-N676D (IC50 = 6.1 nM), BaF3-FLT3-ITD-Y842H (IC50 = 45.5 nM), BaF3-FLT3-ITD-F691L (IC50 = 125.2 nM), BaF3-FLT3-ITD-D835V (IC50 = 177.65 nM) and BaF3-FLT3-ITD-D835Y (IC50 = 220 nM). SILA-123 strongly affected FLT3-ITD mediated signaling pathways and induced apoptosis by arresting cell cycle progression into the G0/G1 phase. Moreover, SILA-123 exhibited superior kinome selectivity against 310 kinases (S score (10) = 0.06). In terms of safety, in vivo evaluations performed on the granulopoiesis of transgenic myeloperoxidase (MPO) zebrafish and mice models have shown an acceptable safety profile for SILA-123. In in vivo studies, SILA-123 displayed an acceptable bioavailability (F% = 21.3%) and significantly suppressed the tumor growth in MV4-11 (50mg/kg/d, TGI = 87.3%) and BaF3-FLT3-ITD-G697R (50 mg/kg/d, TGI = 60.0%) cell-inoculated xenograft models. Our data suggested that SILA-123 might be a promising drug candidate for FLT3 mutant AML.

Background Acute myeloid leukemia (AML) is the most common type of blood cancer. Fmslike tyrosine kinase 3 (FLT3) is a member of the class III receptor tyrosine kinase family. Overexpression of FLT3 was found in 70-100% of patients with acute myeloid leukaemia. FLT3 internal tandem duplication alteration (ITD) and the tyrosine kinase domain (TKD) are the most common molecular alteration in AML, and FLT3 has become a promising drug target for AML. Objective A series of 6-phenylisoxazolo[3,4-b]pyridin-3-amine derivatives F1–F15 with amide bonds as FLT3 inhibitors were designed and synthesized in order to find a new lead compound to treat AML. Methods We designed an original scaffold-hopping protocol by combing the RECAP tool with the Gilde-Based Core-Hopping tool to design novel FLT3 inhibitors based on Linifanib. Inhibitors assembled were ranked by the docking scores generated by Glide. Compounds undisclosed among the top 10 were selected to design a series of 6-phenylisoxazolo[3,4-b]pyridin-3-amine derivatives as FLT3 inhibitors. The kinase inhibitory activities of the fifteen compounds were assayed on FLT3 and FLT3-ITD. The antitumor activities of the structurally modified compounds F1–F15 were evaluated against MOLM-13 and MV4-11, typical FLT3-dependent human AML cells carrying FLT3-ITD mutants and the FLT3- independent human cervical carcinoma cell line HL-60 (harboring wide-type FLT3). Results Structure–activity relationship (SAR) analysis showed that F14 could inhibit FLT3 and FLT3- ITD by 52% and 45.55%, respectively, at the concentration of 1 mΜ. F14 exhibited potent activity against FLT3-dependent human acute myeloid leukemia (AML) cell lines, MOLM-13, and MV4-11 (harboring FLT3-ITD mutant) with IC50 values of 2.558 μM and 1.785 μM, respectively. Conclusion F14 could be used as a novel lead compound to further develop FLT3 inhibitors against AML with FLT3-ITD mutant.