Discovery of RORγ Allosteric Fluorescent Probes and Their Application: Fluorescence Polarization, Screening, and Bioimaging.

Retinoic acid receptor-related orphan receptor γ (RORγ) acts as a crucial transcription factor in Th17 cells and is involved in diverse autoimmune disorders. RORγ allosteric inhibitors have gained significant research focus as a novel strategy to inhibit RORγ transcriptional activity. Leveraging the high affinity and selectivity of RORγ allosteric inhibitor MRL-871 (1), this study presents the design, synthesis, and characterization of 11 allosteric fluorescent probes. Utilizing the preferred probe 12h, we established an efficient and cost-effective fluorescence polarization-based affinity assay for screening RORγ allosteric binders. By employing virtual screening in conjunction with this assay, 10 novel RORγ allosteric inhibitors were identified. The initial SAR studies focusing on the hit compound G381-0087 are also presented. The encouraging outcomes indicate that probe 12h possesses the potential to function as a powerful tool in facilitating the exploration of RORγ allosteric inhibitors and furthering understanding of RORγ function.

Immune-related long noncoding RNA zinc finger protein 710-AS1-201 promotes the metastasis and invasion of gastric cancer cells.

BACKGROUND: Gastric cancer (GC) is a prevalent malignant tumor of the gastrointestinal system. ZNF710 is a transcription factor (TF), and zinc finger protein 710 (ZNF710)-AS1-201 is an immune-related long noncoding RNA (lncRNA) that is upregulated in GC cells. AIM: To assess the correlation between ZNF710-AS1-201 and immune microenvironment features and to investigate the roles of ZNF710-AS1-201 in the invasion and metastasis processes of GC cells. METHODS: We obtained data from The Cancer Genome Atlas and Wujin Hospital. We assessed cell growth, migration, invasion, and programmed cell death using cell counting kit-8, EdU, scratch, Transwell, and flow cytometry assays. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to identify the potential downstream targets of ZNF710-AS1-201. RESULTS: In GC tissues with low ZNF710-AS1-201 expression, immunoassays detected significant infiltration of various antitumor immune cells, such as memory CD8 T cells and activated CD4 T cells. In the low-expression group, the half-maximal inhibitory concentrations (IC50s) of 5-fluorouracil, cisplatin, gemcitabine, and trametinib were lower, whereas the IC50s of dasatinib and vorinostat were higher. The malignant degree of GC was higher and the stage was later in the high-expression group. Additionally, patients with high expression of ZNF710-AS1-201 had lower overall survival and disease-free survival rates. In vitro, the overexpression of ZNF710-AS1-201 greatly enhanced growth, metastasis, and infiltration while suppressing cell death in HGC-27 cells. In contrast, the reduced expression of ZNF710-AS1-201 greatly hindered cell growth, enhanced apoptosis, and suppressed the metastasis and invasion of MKN-45 cells. The expression changes in ZNF710 were significant, but the corresponding changes in isocitrate dehydrogenase-2, Semaphorin 4B, ARHGAP10, RGMB, hsa-miR-93-5p, and ZNF710-AS1-202 were not consistent or statistically significant after overexpression or knockdown of ZNF710-AS1-201, as determined by qRT-PCR. CONCLUSION: Immune-related lncRNA ZNF710-AS1-201 facilitates the metastasis and invasion of GC cells. It appears that ZNF710-AS1-201 and ZNF710 have potential as effective targets for therapeutic intervention in GC. Nevertheless, it is still necessary to determine the specific targets of the ZNF710 TF.

Genome assembly of autotetraploid Actinidia arguta highlights adaptive evolution and enables dissection of important economic traits.

Actinidia arguta, the most widely distributed Actinidia species and the second cultivated species in the genus, can be distinguished from the currently cultivated Actinidia chinensis on the basis of its small and smooth fruit, rapid softening, and excellent cold tolerance. Adaptive evolution of tetraploid Actinidia species and the genetic basis of their important agronomic traits are still unclear. Here, we generated a chromosome-scale genome assembly of an autotetraploid male A. arguta accession. The genome assembly was 2.77 Gb in length with a contig N50 of 9.97 Mb and was anchored onto 116 pseudo-chromosomes. Resequencing and clustering of 101 geographically representative accessions showed that they could be divided into two geographic groups, Southern and Northern, which first diverged 12.9 million years ago. A. arguta underwent two prominent expansions and one demographic bottleneck from the mid-Pleistocene climate transition to the late Pleistocene. Population genomics studies using paleoclimate data enabled us to discern the evolution of the species' adaptation to different historical environments. Three genes (AaCEL1, AaPME1, and AaDOF1) related to flesh softening were identified by multi-omics analysis, and their ability to accelerate flesh softening was verified through transient expression assays. A set of genes that characteristically regulate sexual dimorphism located on the sex chromosome (Chr3) or autosomal chromosomes showed biased expression during stamen or carpel development. This chromosome-level assembly of the autotetraploid A. arguta genome and the genes related to important agronomic traits will facilitate future functional genomics research and improvement of A. arguta.

Dynamical characteristics of honeycomb two-dimensional gyroscopic metamaterials.

Suppression of noise and vibration suppression is important in various fields, such as the living environment, industrial development, and national defense and security. The bandgap properties of phononic crystal metamaterials provide an approach for controlling and eliminating harmful vibrations in equipment and noise in the environment. In this study, we used two types of two-dimensional honeycomb gyroscopic metamaterials: free and constrained. The dynamic equations of the two systems were established using angular momentum and Lagrange theorems. The dispersion relations of the two systems were obtained based on the Bloch theorem, and the influence of the gyroscope angular momentum or gyroscope speed on the dispersion relations was analyzed. Numerical simulations were conducted to analyze the wave propagation characteristics and polarization under different excitation conditions in a limited space for both types of metamaterial structures. The constrained-type and free-type metamaterials were compared, and the regularities of the dispersion relations and wave propagation characteristics by the gyroscope effect were summarized. This study provided a comprehensive and in-depth understanding of the bandgap and wave propagation properties of gyroscopic metamaterials and provided ideas for the design of bandgap modulation in metamaterials.

Design and synthesis 1H-Pyrrolo[2,3-b]pyridine derivatives as FLT3 inhibitors for the treatment of Acute myeloid Leukemia.

Acute myeloid leukemia (AML) is the most common type of blood cancer and has been strongly correlated with the overexpression of Fms-like tyrosine kinase 3 (FLT3), a member of the class III receptor tyrosine kinase family. With the emergence of FLT3 internal tandem duplication alteration (ITD) and tyrosine kinase domain (TKD) mutations, the development of FLT3 small molecule inhibitors has become an effective medicinal chemistry strategy for AML. Herein, we have designed and synthesized two series of 1H-pyrrolo[2,3-b]pyridine derivatives CM1-CM24, as FLT3 inhibitors based on F14, which we previously reported, that can target the hydrophobic FLT3 back pocket. Among these derivates, CM5 showed significant inhibition of FLT3 and FLT3-ITD, with inhibitory percentages of 57.72 % and 53.77 % respectively at the concentration of 1 µΜ. Furthermore, CM5 demonstrated potent inhibition against FLT3-dependent human AML cell lines MOLM-13 and MV4-11 (both harboring FLT3-ITD mutant), with IC50 values of 0.75 µM and 0.64 µM respectively. In our cellular mechanistic studies, CM5 also effectively induces apoptosis by arresting cell cycle progression in the G0/G1 phase. In addition, the amide and urea linker function were discussed in detail based on computational simulations studies. CM5 will serve as a novel lead compound for further structural modification and development of FLT3 inhibitors specifically targeting AML with FLT3-ITD mutations.

Generation of the human induced pluripotent stem cell line PUMCi005-A from a patient with Perrault syndrome.

We generated PUMCi005-A, an induced pluripotent stem cell (iPSC) line, from dermal fibroblasts of a 32-year-old female Perrault syndrome patient with double heterozygous (794 G > A and 1181 G > A) mutations in the TWNK gene using Sendai viral delivery of OCT4, SOX2, KLF4, and c-MYC. The PUMCi005-A iPSC line carried the TWNK mutations, displayed typical iPSC morphology, expressed pluripotent stem cell markers, did not have integration of Sendai virus, and exhibited a normal karyotype and differentiation into three germ layers.

Unveiling the Occurrence and Non-Negligible Role of Amino Sugars in Waste Activated Sludge Fermentation by an Enriched Chitin-Degradation Consortium.

Polysaccharides in extracellular polymeric substances (EPS) can form a hybrid matrix network with proteins, impeding waste-activated sludge (WAS) fermentation. Amino sugars, such as N-acetyl-d-glucosamine (GlcNAc) polymers and sialic acid, are the non-negligible components in the EPS of aerobic granules or biofilm. However, the occurrence of amino sugars in WAS and their degradation remains unclear. Thus, amino sugars (∼6.0%) in WAS were revealed, and the genera of Lactococcus and Zoogloea were identified for the first time. Chitin was used as the substrate to enrich a chitin-degrading consortium (CDC). The COD balances for methane production ranged from 83.3 and 95.1%. Chitin was gradually converted to oligosaccharides and GlcNAc after dosing with the extracellular enzyme. After doing enriched CDC in WAS, the final methane production markedly increased to 60.4 ± 0.6 mL, reflecting an increase of ∼62%. Four model substrates of amino sugars (GlcNAc and sialic acid) and polysaccharides (cellulose and dextran) could be used by CDC. Treponema (34.3%) was identified as the core bacterium via excreting chitinases (EC 3.2.1.14) and N-acetyl-glucosaminidases (EC 3.2.1.52), especially the genetic abundance of chitinases in CDC was 2.5 times higher than that of WAS. Thus, this study provides an elegant method for the utilization of amino sugar-enriched organics.

Effect of Asymmetry on the Contact Time of Droplet Impact on Superhydrophobic Cylindrical Surfaces.

Reducing the contact time during the droplet impact on the surface is crucial for anti-icing, self-cleaning, and heat transfer optimization applications. This study aims to minimize the contact time by modifying the surface curvature to create an asymmetric impact process. Our experiments showed that the increase in Weber numbers (We) and the decrease in the ratio of surface diameter to droplet diameter (D*) intensify the asymmetry of the impact process, yielding four distinct rebound modes. Low asymmetry observes the liquid retract toward the central point (Rebound Modes 1 and 2), whereas high asymmetry yields a wing-like rebound (Rebound Modes 3 and 4). In Rebound Mode 1, increased asymmetry would lead to more extended contact due to the prolonged waiting period. Conversely, the reduction in contact time in Rebound Mode 2 occurs due to increased asymmetry with no waiting period. For Rebound Modes 3 and 4, the retraction time could be divided into three stages, generated by two liquid detachment modes from the surface. Analysis reveals that an increased asymmetry would reduce the retraction time during the first stage but prolong it during the third stage, with no significant effects on the second. Four correlations, each pertaining to a distinct impact mode, are proposed based on these analyses to describe the contact time concerning We and D* for droplets impacting a superhydrophobic cylindrical surface.

Ir/Zn-cocatalyzed chemo- and atroposelective [2+2+2] cycloaddition for construction of C─N axially chiral indoles and pyrroles.

Here, an Ir/Zn-cocatalyzed atroposelective [2+2+2] cycloaddition of 1,6-diynes and ynamines was developed, forging various functionalized C─N axially chiral indoles and pyrroles in generally good to excellent yields (up to 99%), excellent chemoselectivities, and high enantioselectivities (up to 98% enantiomeric excess) with wide substrate scope. This cocatalyzed strategy not only provided an alternative promising and reliable way for asymmetric alkyne [2+2+2] cyclotrimerization in an easy handle but also settled the issues of previous [Rh(COD)2]BF4-catalyzed system on the construction of C─N axial chirality such as complex operations, limited substrate scope, and low efficiency. In addition, control experiments and theoretical calculations disclosed that Zn(OTf)2 markedly reduced the barrier of migration insertion to significantly increase reaction efficiency, which was distinctly different from previous work on the Lewis acid for improving reaction yield through accelerating oxidative addition and reductive elimination.

Working Regime Criteria for Microscale Electrohydrodynamic Conduction Pumps.

We investigated the microscale electrohydrodynamic (EHD) conduction pumps in a wide range of working regimes, from the saturation regime to the ohmic regime. We showed that the existing macro- and microscale theoretical models could not accurately predict the electric force of microscale EHD conduction pumps, especially for the cases of a strong diffusion effect. We clarified that the failure is caused by a rough estimate of the heterocharge layer thickness. We revised the expression of heterocharge layer thickness by considering the diffusion effect and developed a new theoretical model for the microscale EHD conduction pumps based on the revised expression of heterocharge layer thickness. The results showed that our model can accurately predict the dimensionless electric force of the microscale EHD conduction pumps even for the cases of a strong diffusion effect. Furthermore, we developed a working regime map of microscale EHD conduction pumps and found that the microscale EHD conduction pumps more easily fall into the saturation regime compared with the macroscale EHD conduction pumps due to the enhanced diffusion effect; in other words, the microscale EHD conduction pumps have a wider saturation regime. We showed that the conduction number C0 could not distinguish the working regime of the microscale EHD conduction pumps because it does not take the diffusion effect into account. By employing the revised expression of heterocharge layer thickness, we proposed a new dimensionless number, C0D to distinguish the working regimes of microscale EHD conduction pumps.

Preclinical characterization of danatinib as a novel FLT3 inhibitor with excellent efficacy against resistant acute myeloid leukemia.

The therapeutic benefits of available FLT3 inhibitors for AML are limited by drug resistance, which is related to mutations, as well toxicity caused by off-target effects. In this study, we introduce a new small molecule FLT3 inhibitor called danatinib, which was designed to overcome the limitations of currently approved agents. Danatinib demonstrated greater potency and selectivity, resulting in cytotoxic activity specific to FLT3-ITD and/or FLT3-TKD mutated models. It also showed a superior kinome inhibition profile compared to several currently approved FLT3 inhibitors. In diverse FLT3-TKD models, danatinib exhibited substantially improved activity at clinically relevant doses, outperforming approved FLT3 inhibitors. In vivo safety evaluations performed on the granulopoiesis of transgenic myeloperoxidase (MPO) zebrafish and mice models proved danatinib to have an acceptable safety profile. Danatinib holds promise as a new and improved FLT3 inhibitor for the treatment of AML, offering long-lasting remissions and improved overall survival rates.

Suppression of SAMSN1 contributes to neuroprotection in neonatal rats suffering from hypoxic-ischemic encephalopathy injury.

This article aims to detect the effect of SAM domain, SH3 domain, and nuclear localization signal 1 (SAMSN1) in neonatal rats with neurological dysfunction induced by hypoxia and ischemia (HI). The HI model was created using 7-day postnatal rats. Zea-longa score was utilized to validate the neurological injury after HI. Then, the differentially expressed genes (DEGs) were detected by gene sequencing and bioinformatics analysis methods. The oxygen and glucose deprivation (OGD) models were established in the SY5Y cells and fetal human cortical neurons. In addition, SAMSN1-small interfering RNA, methyl thiazolyl tetrazolium assay, and cell growth curve were employed to evaluate the cell viability variation. Obviously, Zea-longa scores increased in rats with HI insult. Subsequently, SAMSN1 was screened out, and it was found that SAMSN1 was strikingly upregulated in SY5Y cells and fetal neurons post-OGD. Interestingly, we found that SAMSN1 silencing could markedly enhance cell viability and cell growth after OGD. These data suggested that downregulation of SAMSN1 may exert a neuroprotective effect on damaged neurons after HI by improving cell viability and cell survival, which provides a potential theoretical basis for clinical trials in the future to treat neonatal hypoxic-ischemic encephalopathy.

Glucose status within dark-grown etiolated cotyledons determines seedling de-etiolation upon light irradiation.

Exposure of dark-grown etiolated seedlings to light triggers the transition from skotomorphogenesis/etiolation to photomorphogenesis/de-etiolation. In the life cycle of plants, de-etiolation is essential for seedling development and plant survival. The mobilization of soluble sugars (glucose [Glc], sucrose, and fructose) derived from stored carbohydrates and lipids to target organs, including cotyledons, hypocotyls, and radicles, underpins de-etiolation. Therefore, dynamic carbohydrate biochemistry is a key feature of this phase transition. However, the molecular mechanisms coordinating carbohydrate status with the cellular machinery orchestrating de-etiolation remain largely opaque. Here, we show that the Glc sensor HEXOKINASE 1 (HXK1) interacts with GROWTH REGULATOR FACTOR5 (GRF5), a transcriptional activator and key plant growth regulator, in Arabidopsis (Arabidopsis thaliana). Subsequently, GRF5 directly binds to the promoter of phytochrome A (phyA), encoding a far-red light (FR) sensor/cotyledon greening inhibitor. We demonstrate that the status of Glc within dark-grown etiolated cotyledons determines the de-etiolation of seedlings when exposed to light irradiation by the HXK1-GRF5-phyA molecular module. Thus, following seed germination, accumulating Glc within dark-grown etiolated cotyledons stimulates a HXK1-dependent increase of GRF5 and an associated decrease of phyA, triggering the perception, amplification, and relay of HXK1-dependent Glc signaling, thereby facilitating the de-etiolation of seedlings following light irradiation. Our findings, therefore, establish how cotyledon carbohydrate signaling under subterranean darkness is sensed, amplified, and relayed, determining the phase transition from skotomorphogenesis to photomorphogenesis on exposure to light irradiation.

What Controls the Hole Formation of Nanodroplets: Hydrodynamic or Thermodynamic Instability?

Using molecular dynamics simulations, we investigate the air hole formation of water nanodroplets impacting hydrophilic to hydrophobic surfaces in the range of static contact angles from 30° to 140° with different initial surface temperatures ranging from 300 to 1000 K. We show that the hole dynamics of nanodroplets are different from those observed in millimeter-sized droplets. The hole formation can be observed on smooth surfaces for nanodroplets; however, it only occurs on nonsmooth surfaces for millimeter-sized droplets. We clarify that the hole formation of nanodroplets is triggered by a nucleated vapor bubble due to thermodynamic instability, whereas it is initiated by air bubble entrapment during impact due to hydrodynamic instability for millimeter-sized droplets. The hole formation of nanodroplets relies heavily on the surface temperature and surface wettability, because the nucleated vapor bubble more easily occurs and grows on the surface with high initial temperatures and hydrophobic surfaces. Based on the thermal stability analysis, a criterion is developed to predict the hole formation of nanodroplets, which verifies the dependence of hole formation on the surface temperature and wettability. Furthermore, we show that the ring-bouncing of nanodroplets is triggered by the nucleated vapor bubble. We clarify the reasons for the reduced contact time of nanodroplets caused by the ring-bouncing.

Natural products as potential lead compounds to develop new antiviral drugs over the past decade.

Virus infection has been one of the main causes of human death since the ancient times. Even though more and more antiviral drugs have been approved in clinic, long-term use can easily lead to the emergence of drug resistance and side effects. Fortunately, there are many kinds of metabolites which were produced by plants, marine organisms and microorganisms in nature with rich structural skeletons, and they are natural treasure house for people to find antiviral active substances. Aiming at many types of viruses that had caused serious harm to human health in recent years, this review summarizes the natural products with antiviral activity that had been reported for the first time in the past ten years, we also sort out the source, chemical structure and safety indicators in order to provide potential lead compounds for the research and development of new antiviral drugs.

Aging rate, environmental risk and production efficiency of the low-density polyethylene (LDPE) films with contrasting thickness in irrigated region.

Physical thickness of low-density polyethylene (LDPE) films might determine the release rate of phthalic acid esters (PAEs) & structural integrity and affect production efficiency. However, this critical issue is still unclear and little reported. Aging effects were evaluated in LDPE films with the thickness of 0.006, 0.008, 0.010 and 0.015 mm in a maize field of irrigation region. The Scanning electron microscope (SEM) results showed that the proportion of damaged area (Dam) to total area of LDPE films was massively lowered with increasing thickness after aging. The highest and lowest Dam was 32.2% and 3.5% in 0.006 and 0.015 mm films respectively. Also, the variations in peak intensity of asymmetric & symmetrical stretching vibrations (ASVI & SSVI) were detected using Fourier transform infrared spectrum (FTIR), indicating that the declines in peak intensity tended to be slower with thickness. Interestingly, the declines in physical integrity were tightly associated with increasing exhalation rate of PAEs. Average releasing rate of PAEs was 38.2%, 31.4%, 31.5% and 19.7% in LDPE films from 0.006 to 0.015 mm respectively. Critically, thicker film mulching can lead to greater soil water storage at plough layer (SWS-PL) and better thermal status, accordingly harvesting higher economic benefit. Therefore, LDPE film thickening may be a solution to reduce environmental risk but improve production efficiency in arid region.

Farmers' participation into the recovery of waste agricultural plastic film: An application of the Theory of Planned Behavior.

This study aims to address the lack of relevant researches in the field of waste recycling using the Theory of Planned Behavior (TPB). A village-scale social survey was conducted to investigate the degree of farmers' participation in a waste plastic film program, i.e. Old for New in northwest China. The program required farmers to recycle plastic film residues in exchange for new films. Survey results showed that 67.5% of farmers accepted the program, yet only 14.5% of them actually participated. Logistic regression analysis was used to analyze questionnaire data and identify the factors that significantly affected farmers' recycling behavior. Principal component and weight analysis further showed that farmers' participation was mainly influenced by their attitudes (p < 0.01), with a relative weight (RW) of 46.3%. Yet, subjective norms (p < 0.1) and perceived behavior control (p < 0.1) had less effect on the degree of participation, and their RWs were 4.2% and 4.1% only, respectively. Moreover, the RW of plastic film usage characteristics and household characteristics reached up to 13.2% and 6.4%, respectively. Interestingly, environmental awareness (ß = 0.083) and compulsory environmental education (ß = 0.130) as surface factors strongly affected the farmers' adoption and response, with the RW of 25.7%. As such, the extended TPB model was established to analyze the participation behavior of farmers for stronger explanatory power. This study highlighted a promising strategy based on TPB for waste plastic film recycling and similar environmental management practices.

Intraoperative Low-Dose S-Ketamine Reduces Depressive Symptoms in Patients with Crohn's Disease Undergoing Bowel Resection: A Randomized Controlled Trial.

Background: Patients with Crohn's disease (CD) undergoing bowel resection often suffer from depression and acute pain, which severely impairs their recovery. We aimed to investigate the effects of S-ketamine preconditioning on postoperative depression in patients with CD undergoing a bowel resection with mild to moderate depression and to observe whether it can relieve postoperative pain and anti-inflammation. Methods: A total of 124 adult patients were randomized into one of the two groups. Patients in the S-ketamine group received a 0.25 mg/kg S-ketamine intravenous drip under general anesthesia induction, followed by a continuous infusion of S-ketamine with 0.12 mg/kg/h for more than 30 min through target-controlled infusion. Patients in the placebo group received 0.9% saline at an identical volume and rate. The primary outcome measure was the 17-item Hamilton depression Scale (HAMD-17). The secondary outcomes were scores on the following questionnaires: a nine-item patient health questionnaire (PHQ-9); a quality of recovery (QoR-15) form; and a numeric rating scale (NRS). Additional secondary outcomes included the levels of C-reactive protein (CRP) and interleukin 6 (IL-6) on postoperative days (PODs) 1, 3, and 5, the length of hospital stay, and opioid use throughout the hospital stay. Results: The scores of PHQ-9 and HAMD-17 in the S-ketamine group were lower than those in the placebo group on postoperative days (PODs) 1, 2, and 7 (p < 0.05). The scores of QoR-15 in the S-ketamine group were higher than those in the placebo group on postoperative days (PODs) 3 and 5 (p < 0.05). The NRS scores of PACU, postoperative days 1 and 2 in the S-ketamine group were lower than those in the placebo group (p < 0.05). There was no significant difference in the CRP and IL-6 levels on postoperative days (PODs) 1, 3, and 5, postoperative complications, and hospital stay between the two groups (p > 0.05). Conclusions: The trial indicated that the intraoperative administration of low-dose S-ketamine could alleviate mild-to-moderate depressive symptoms and postoperative pain in patients with Crohn's disease undergoing bowel resection without worsening their safety.

Discovery of 4-(4-aminophenyl)-6-phenylisoxazolo[3,4-b]pyridine-3-amine derivatives as novel FLT3 covalent inhibitors for the intervention of acute myeloid leukemia.

Small molecule covalent drugs have proved to be desirable therapies especially on drug resistance related to point mutations. Secondary mutations of FLT3 have become the main mechanism of FLT3 inhibitors resistance which further causes the failure of treatment. Herein, a series of 4-(4-aminophenyl)-6-phenylisoxazolo[3,4-b]pyridine-3-amine covalent derivatives were synthesized and optimized to overcome the common secondary resistance mutations of FLT3. Among these derivatives, compound F15 displayed potent inhibition activities against FLT3 (IC50 = 123 nM) and FLT3-internal tandem duplication (ITD) by 80% and 26.06%, respectively, at the concentration of 1 µM. Besides, F15 exhibited potent activity against FLT3-dependent human acute myeloid leukemia (AML) cell lines MOLM-13 (IC50 = 253 nM) and MV4-11 (IC50 = 91 nM), as well as BaF3 cells with variety of secondary mutations. Furthermore, cellular mechanism assays indicated that F15 inhibited phosphorylation of FLT3 and its downstream signaling factors. Notably, F15 could be considered for further development as potential drug candidate to treat AML.