Study on Tin-Cobalt Bimetallic Phosphide Nanoparticles as a Negative Electrode of Sodium-Ion Batteries.

Tin phosphide (Sn4P3) holds great promise because sodium-ion batteries use this material as an anode with impressive theoretical capacity. In this paper, it is reported that Co-doped Sn4P3 is embedded into carbon-based materials and SnCoP/C with a porous skeleton is prepared. As a result, SnCoP/C-2, as the material utilized in sodium-ion battery anodes, exhibits reversible capacities at 415.6, 345.9, and 315.6 mAh g-1 at current intensities of 0.5, 1.0, and 2.0 A g-1, respectively. The electrochemical reversibility, cycle stability, and rate performance of SnCoP/C samples are obviously better than those of Sn4P3/C. Cobalt in SnCoP/C stabilizes the conductive matrix of tin phosphide and promotes the diffusion kinetics of sodium. These results show that, with an appropriate amount of cobalt doping, highly dispersed nanoparticles can be formed in the tin phosphide matrix, which can significantly enhance the cycle stability of tin-based electrode materials.

QSAR Study, Molecular Docking and Molecular Dynamic Simulation of Aurora Kinase Inhibitors Derived from Imidazo[4,5-b]pyridine Derivatives.

Cancer is a serious threat to human life and social development and the use of scientific methods for cancer prevention and control is necessary. In this study, HQSAR, CoMFA, CoMSIA and TopomerCoMFA methods are used to establish models of 65 imidazo[4,5-b]pyridine derivatives to explore the quantitative structure-activity relationship between their anticancer activities and molecular conformations. The results show that the cross-validation coefficients q2 of HQSAR, CoMFA, CoMSIA and TopomerCoMFA are 0.892, 0.866, 0.877 and 0.905, respectively. The non-cross-validation coefficients r2 are 0.948, 0.983, 0.995 and 0.971, respectively. The externally validated complex correlation coefficients r2pred of external validation are 0.814, 0.829, 0.758 and 0.855, respectively. The PLS analysis verifies that the QSAR models have the highest prediction ability and stability. Based on these statistics, virtual screening based on R group is performed using the ZINC database by the Topomer search technology. Finally, 10 new compounds with higher activity are designed with the screened new fragments. In order to explore the binding modes and targets between ligands and protein receptors, these newly designed compounds are conjugated with macromolecular protein (PDB ID: 1MQ4) by molecular docking technology. Furthermore, to study the nature of the newly designed compound in dynamic states and the stability of the protein-ligand complex, molecular dynamics simulation is carried out for N3, N4, N5 and N7 docked with 1MQ4 protease structure for 50 ns. A free energy landscape is computed to search for the most stable conformation. These results prove the efficient and stability of the newly designed compounds. Finally, ADMET is used to predict the pharmacology and toxicity of the 10 designed drug molecules.

Structure-based virtual screening of novel USP5 inhibitors targeting the zinc finger ubiquitin-binding domain.

The equilibrium of cellular protein levels is pivotal for maintaining normal physiological functions. USP5 belongs to the deubiquitination enzyme (DUBs) family, controlling protein degradation and preserving cellular protein homeostasis. Aberrant expression of USP5 is implicated in a variety of diseases, including cancer, neurodegenerative diseases, and inflammatory diseases. In this paper, a multi-level virtual screening (VS) approach was employed to target the zinc finger ubiquitin-binding domain (ZnF-UBD) of USP5, leading to the identification of a highly promising candidate compound 0456-0049. Molecular dynamics (MD) simulations were then employed to assess the stability of complex binding and predict hotspot residues in interactions. The results indicated that the candidate stably binds to the ZnF-UBD of USP5 through crucial interactions with residues ARG221, TRP209, GLY220, ASN207, TYR261, TYR259, and MET266. Binding free energy calculations, along with umbrella sampling (US) simulations, underscored a superior binding affinity of the candidate relative to known inhibitors. Moreover, US simulations revealed conformational changes of USP5 during ligand dissociation. These insights provide a valuable foundation for the development of novel inhibitors targeting USP5.

Indazolin-3-ylidenes (Indy*): easily accessible, sterically-hindered indazole-derived N-heterocyclic carbenes and their application in gold catalysis.

Sterically-hindered N-heterocyclic carbenes (NHCs) with functionalized N-wingtips are a pivotal class of ligands in organic synthesis. Herein, we report the first class of sterically-hindered N-heterocyclic carbenes based on the indazole framework. These ligands combine the strong σ-donation of the carbene center due to the carbene placement at the C3-indazole position with the sterically-hindered and flexible N-substitution with the versatile 2,6-bis(diphenylmethyl)aryl moiety that extends beyond the metal centre for the first time in non-classical N-heterocyclic carbenes. The ligands are readily accessible by the rare Cadogan indazole synthesis of sterically-hindered N-aryl-1-(2-nitrophenyl)methanimines. Steric and electronic characterization as well as catalytic studies in the synthesis of oxazolines are described. Considering the unique properties of indazole-derived carbenes, we anticipate that this class of compounds will find broad application in organic synthesis and catalysis.

Fe-modified NASICON-type Na3V2(PO4)3 as a cathode material for sodium ion batteries.

The sol-gel method is used to synthesize a new compound called Na3Fe0.8V1.2(PO4)3/C (NFVP/C), which has a crystal structure and belongs to the NASICON-type family. The dimensions of NFVP's unit cell are a = 8.717 (1) Å, c = 21.84 (1) Å, and V = 1437.27 (0) Å3. The Na‖NFVP/C battery provides a discharge potential of 3.43 V compared to Na+/Na, an intriguing rate capability of 76.2 mA h g-1 at 40C, and maintains an impressive capacity of 97.8% after 500 cycles at 5C. The excellent efficiency of Na3Fe0.8V1.2(PO4)3/C can be ascribed to its elevated Na+ conductivity and reduced energy barrier for sodium-ion diffusion. The NASICON-type Na3Fe0.8V1.2(PO4)3/C is a promising material for sodium-ion batteries.

Combining QSAR techniques, molecular docking, and molecular dynamics simulations to explore anti-tumor inhibitors targeting Focal Adhesion Kinase.

Focal Adhesion Kinase (FAK) is an important target for tumor therapy and is closely related to tumor cell genesis and progression. In this paper, we selected 46 FAK inhibitors with anticancer activity in the pyrrolo pyrimidine backbone to establish 3D/2D-QSAR models to explore the relationship between inhibitory activity and molecular structure. We have established two ideal models, namely, the Topomer CoMFA model (q2= 0.715, r2= 0.984) and the Holographic Quantitative Structure-Activity Relationship (HQSAR) model (q2= 0.707, r2= 0.899). Both models demonstrate excellent external prediction capabilities.Based on the QSAR results, we designed 20 structurally modified novel compounds, which were subjected to molecular docking and molecular dynamics studies, and the results showed that the new compounds formed many robust interactions with residues within the active pocket and could maintain stable binding to the receptor proteins. This study not only provides a powerful screening tool for designing novel FAK inhibitors, but also presents a series of novel FAK inhibitors with high micromolar activity that can be used for further characterization. It provides a reference for addressing the shortcomings of drug metabolism and drug resistance of traditional FAK inhibitors, as well as the development of novel clinically applicable FAK inhibitors.Communicated by Ramaswamy H. Sarma.

Talaromyces marneffei infection with IFNGR1 gene mutation in a patient with negative Anti-Interferon-γ autoantibodies.

BACKGROUND: Talaromyces Marneffei (TM) is a rare opportunistic pathogen that mostly infects patients with low immunity compared to those with normal immunity. It may be related to immune deficiency or genetic factors. OBJECTIVE: To evaluate the gene mutation of a patient infected with TM in an endemic area with negative anti-interferon-γ autoantibodies, and negative human immunodeficiency virus (HIV) infection. METHODS: Extract deoxyribonucleic acid (DNA) samples from the patient's peripheral blood, detect the mutation gene by whole exome sequencing (WES), and carry out Sanger sequencing verification for the detected mutation gene. RESULTS: The authors detected a mutation in the IFNGR1 gene (NM_001363526.1) and validated the detected gene mutation using Sanger sequencing. The results showed a heterozygous mutation c.4C>T (p.L2F) located in the IFNGR1 gene (NM_001363526.1). STUDY LIMITATIONS: The mechanism of the IFNGR1 gene has not been further investigated in this study. CONCLUSIONS: The IFNGR1 gene mutation may be a potential risk factor for TM infection, and the presence of anti-interferon-γ autoantibodies can aggravate disease symptoms.

Dissecting the role of ALK double mutations in drug resistance to lorlatinib with in-depth theoretical modeling and analysis.

Anaplastic lymphoma kinase (ALK) is implicated in the genesis of multiple malignant tumors. Lorlatinib stands out as the most advanced and effective inhibitor currently used in the clinic for the treatment of ALK-positive non-small cell lung cancer. However, resistance to lorlatinib has inevitably manifested over time, with double/triple mutations of G1202, L1196, L1198, C1156 and I1171 frequently observed in clinical practice, and tumors regrow within a short time after treatment with lorlatinib. Therefore, elucidating the mechanism of resistance to lorlatinib is paramount in paving the way for innovative therapeutic strategies and the development of next-generation drugs. In this study, we leveraged multiple computational methodologies to delve into the resistance mechanisms of three specific double mutations of ALKG1202R/L1196M, ALKG1202R/L1198F and ALKI1171N/L1198F to lorlatinib. We analyzed these mechanisms through qualitative (PCA, DCCM) and quantitative (MM/GBSA, US) kinetic analyses. The qualitative analysis shows that these mutations exert minimal perturbations on the conformational dynamics of the structural domains of ALK. The energetic and structural assessments show that the van der Waals interactions, formed by the conserved residue Leu1256 within the ATP-binding site and the residues Glu1197 and Met1199 in the hinge domain with lorlatinib, play integral roles in the occurrence of drug resistance. Furthermore, the US simulation results elucidate that the pathways through which lorlatinib dissociates vary across mutant systems, and the distinct environments during the dissociation process culminate in diverse resistance mechanisms. Collectively, these insights provide important clues for the design of novel inhibitors to combat resistance.

Effect of 5-Aminolevulinic Acid Photodynamic Therapy on Aspergillus fumigatus Biofilms in Vitro.

Aspergillus fumigatus biofilm development results in enhanced pathogenicity and treatment resistance. Most contemporary antibiotics, however, are unable to eliminate biofilms. In recent years, with the application of new photosensitizers and the development of treatment, ALA-PDT (5-aminolevulinic acid photodynamic treatment) has achieved remarkable curative effect in the treatment of fungal infectious diseases; however, no research has been conducted on ALA-PDT against A. fumigatus. This study investigated the inhibitory effect of ALA-PDT at various 5-aminolevulinic acid concentrations and light doses on A. fumigatus planktonic and biofilms in vitro. We found that ALA-PDT may successfully inhibit the development of A. fumigatus biofilm and disintegrate mature biofilm. After ALA-PDT treatment, the adherence rate and vitality dramatically decreased, and the biofilm's structure was severely compromised. Our findings show for the first time that ALA-PDT may be used to prevent the formation of A. fumigatus biofilm and disturb the structure of mature biofilm, and that it could be employed as a therapeutic therapy for A. fumigatus superficial infection.

In silico screening and computational evaluation of novel promising USP14 inhibitors targeting the palm-thumb pocket.

Protein degradation and synthesis are essential for regulating various biological activities within the body. As a member of deubiquitinating enzymes (DUBs), ubiquitin-specific protease 14 (USP14) plays a critical role in regulating protein degradation and maintaining cellular protein homeostasis. However, abnormal expression of USP14 has been associated with a variety of malignant tumors and other diseases. In this study, we conducted hierarchical virtual screening against the palm-thumb pocket of USP14, which resulted in the identification of two promising hits with novel scaffolds. We systematically evaluated the potential of these two hits in terms of their binding affinity and selectivity at the computational level. The results indicated that they had stronger binding affinities than previously reported molecules, as evidenced by lower docking scores and binding free energies. The binding stability analysis and hotspot residue prediction based on the MD simulations further revealed that they were capable of stably binding to the palm-thumb pocket of USP14 via crucial interactions with the residues GLN197, TYR476, ASP199, PHE331, TYR436 and HIS426. More importantly, both candidates exhibit higher selectivity for USP14 over several other USP family members (USP5, USP7 and USP15). Our findings are hoped to be a good starting point for the development of selective USP14 inhibitors.

Clinical efficacy of LED golden light combined with acyclovir in the treatment of herpes zoster: a single-center prospective study.

This study aimed to explore the safety and clinical efficacy of light emitting diode (LED) golden light combined with acyclovir in treating herpes zoster (HZ). According to the random number table, 54 inpatients with HZ were divided into control group, golden-light group, and red-light group, with 18 cases in each group. The control group received acyclovir intravenous drip, while the patients in the red-light group received acyclovir intravenous drip and red-light LED phototherapy, and the golden-light group received acyclovir intravenous drip and golden-light LED phototherapy. Primary assessments included herpes stopping time, incrustation time, decrustation time, pain visual analog scale scores (VAS), and incidence of postherpetic neuralgia (PHN) on the 30th and 90th days. Golden-light group and red-light group showed a shorter herpes stopping time, incrustation time, and decrustation time (P < 0.05) compared to the control group (P < 0.05), while the golden-light group showed a shorter incrustation time and decrustation time than the red light group (all P < 0.05). After treatment VAS scores, the golden-light group showed a significant improvement compared to the control group. The golden-light group showed a better PHN incidence than the control group at 30 days follow-up. Compared with the comprehensive curative effect, the total effective rates of the golden-light group, red-light group, and control group were 88.89%, 77.78%, and 72.22%, respectively, and the efficacy of the golden-light group was better than that of the control group and red-light group. Golden light combined with acyclovir can shorten the course of HZ, relieve pain, and reduce the occurrence of PHN, and the effect is better than that of the red-light group and the control group.

Effects of Homogenization Heat Treatment on the Fe Micro-Segregation in Ti-1023 Titanium Alloy.

The segregation of the Fe element in Ti-10V-2Fe-3Al titanium alloy (Ti-1023) can lead to the generation of beta flecks, which seriously affects the performance of Ti-1023 products. During the heat treatment (HT) process at a high temperature, the Fe element in Ti-1023 ingots will migrate, making its distribution more uniform and reducing the segregation index. In this paper, the control of Fe micro-segregation in Ti-1023 ingots by homogenization HT was investigated. Firstly, dissection sampling and SEM-EDS analysis methods were used to study the distribution pattern of the Fe element in the equiaxed grains in the core of Ti-1023 ingots. It was found that the Fe content in the grain gradually increased along with the radial direction from the core to the grain boundary. Then, the homogenization HT experiments and numerical simulations of Ti-1023 at different HT temperatures from 1050 °C to 1200 °C were carried out. The results showed that the uniformity of Fe element distribution within grain can be significantly improved by the homogenization HT. With increasing HT temperature, Fe atoms migration ability increases, and the uniformity of Fe element distribution improves. Homogenization HT at 1150 °C and 1200 °C for 12 h can effectively reduce the degree of Fe element segregation.

Discovery of novel BRD4-BD2 inhibitors via in silico approaches: QSAR techniques, molecular docking, and molecular dynamics simulations.

Bromodomain-containing protein 4(BRD4) plays an important role in the occurrence and development of various malignant tumors, which has attracted the attention of scientific research institutions and pharmaceutical companies. The structural modification of most currently available BRD4 inhibitors is relatively simple, but the drug effectiveness is limited. Research has found that the inhibition of BD1 may promote the differentiation of oligodendrocyte progenitor cell; however, the inhibition of BD2 will not cause this outcome. Therefore, newly potential drugs which target BRD4-BD2 need further research. Herein, we initially built QSAR models out of 49 compounds using HQSAR, CoMFA, CoMSIA, and Topomer CoMFA technology. All of the models have shown suitable reliabilities (q2 = 0.778, 0.533, 0.640, 0.702, respectively) and predictive abilities (r2pred = 0.716, 0.6289, 0.6153, 0.7968, respectively) for BRD4-BD2 inhibitors. On the basis of QSAR results and the search of the R-group in the topomer search module, we designed 20 new compounds with high activity that showed appropriate docking score and suitable ADMET. Docking studies and MD simulation were carried out to reveal the amino acid residues (Asn351, Cys347, Tyr350, Pro293, and Asp299) at the active site of BRD4-BD2. Free energy calculations and free energy landscapes verified the stable binding results and indicated stable conformations of the complexes. These theoretical studies provide guidance and theoretical basis for designing and developing novel BRD4-BD2 inhibitors.

Analysis of clinical features and inflammatory-related molecules with the disease in acute infectious urticaria.

Acute infectious urticaria, a subset of acute urticaria, with severe persistence wheals and systemic symptoms, response well to corticosteroids treatment in combination with antibiotics. The exact pathogenic mechanisms are not fully understood. In this study, we aim to analyze the different clinical features, compare the level of neutrophil activation, and investigate the expression of inflammatory related cytokine in patients with acute urticaria and acute infectious urticaria. Eighteen patients with acute infectious urticaria and eighteen patients with acute urticaria were included in this study. We analyzed the difference between the clinical features and the serum expressions of pro-inflammatory factors in the two groups, then examined the levels of inflammation-associated cytokines before and after treatment of acute infectious urticaria. Hematoxylin & eosin (HE) staining and immunohistochemistry (IHC) were used to further study the relationship between neutrophil and neutrophil-derived Myeloperoxidase (MPO) of lesions in the two groups. The expression levels of C-reactive protein (CRP), D-dimer, interleukin 6 (IL-6), IL-8 and chemokine ligand 8 (CCL8) in serum were significantly higher in acute infectious urticaria than acute urticaria. In acute infectious urticaria, the serum expression levels of CCL8 were significantly decreased after the treatment, a significant correlation observed between CRP levels and IL-6, both CCL8 and CRP were positively correlated with neutrophil granulocytes. Neutrophils infiltration were not observed by HE stains in two groups, but in IHC stains we found a positive expression of MPO in acute infectious urticaria lesions. Elevated neutrophil in the serum, which is associated with the levels of IL-8 & CCL8, and positively expressed MPO in lesions, may be involved in the pathogenic mechanism of acute infectious urticaria.

Interaction of Amiodarone with Azoles Against Aspergillus Planktonic Cells and Biofilms in vitro.

Aspergillus spp. is the most common clinical pathogen of invasive fungal infection with high mortality. Existing treatments for Aspergillus spp. infection are still inefficient and accompanied by drug resistance, so it is still urgent to find new treatment approaches. The antiarrhythmic drug amiodarone (AMD) has demonstrated antifungal activity against a range of fungi. This study evaluated the efficacy of AMD in combination with triazoles for Aspergillus spp. infection. We tested the combined effect of AMD and three triazole drugs, namely, itraconazole (ITR), voriconazole (VRC), and posaconazole (POS), on the planktonic cells and biofilms of 20 strains of Aspergillus spp. via a checkerboard microdilution assay derived from 96-well plate-based method. Our results reveal that the combination of AMD with ITR or POS against Aspergillus biofilms has synergistic fungicidal effects. By contrast, the combination of AMD with VRC exhibits no antagonistic and synergistic effects. In this way, the use of AMD in combination with ITR or POS could be an effective adjunctive treatment for Aspergillus spp. infection.

Successful treatment of tuberculosis verrucosa cutis with fester as primary manifestation with photodynamic therapy and anti-tubercular drugs.

Tuberculosis verrucosa cutis (TBVC) is a rare type of cutaneous tuberculosis, which often occurs in the body with good immunity to tuberculosis bacilli. It usually presents as a hyperkeratotic verrucous plaque with polygonal boarders but can mimic or evolved into other dermatosis such as verruca vulgaris, chromoblastomycosis, hyperkeratotic lupus vulgaris, hypertrophic lichen planus, or squamous cell carcinoma, leading to delayed diagnosis. Here, we reported that a 62-year-old patient diagnosed by TBVC with fester as primary manifestation. Photodynamic therapy combined with anti-tuberculosis drugs is an effective method to treat TBVC lesions with fester, and it may shorten the treatment cycle of anti-tuberculosis drugs.

QSAR analysis of 3-pyrimidin-4-yl-oxazolidin-2-one derivatives isocitrate dehydrogenase inhibitors using Topomer CoMFA and HQSAR methods.

A series of mIDH1 inhibitors derived from 3-pyrimidine-4-oxazolidin-2-ketone derivatives were studied by QSAR model to explore the key factors that inhibit mIDH1 activity. The generated model was cross-verified and non-cross-verified by Topomer CoMFA and HQSAR methods; the independent test set was verified by PLS method; the Topomer search technology was used for virtual screening and molecular design; and the Surflex-Dock method and ADMET technology were used for molecular docking, pharmacology and toxicity prediction of the designed drug molecules. The Topomer CoMFA and HQSAR cross-validation coefficients q2 are 0.783 and 0.784, respectively, and the non-cross-validation coefficients r2 are 0.978 and 0.934, respectively. Ten new drug molecules have been designed using Topomer search technology. The results of molecular docking and ADMET show that the newly designed drug molecules are effective. The docking situation, pharmacology and toxicity prediction results are good. The model can be used to predict the bioactivity of the same type of new compounds and their derivatives. The prediction results of molecular design, molecular docking and ADMET can provide some ideas for the design and development of novel mIDH1 inhibitor anticancer drugs, and provide certain theoretical basis of the experimental verification of new compounds in the future. Newly designed molecules after docking with corresponding proteins in the PDB library, it can explore the targets of drug molecules acting with large proteins and the related force, which is very helpful for the design of new drugs and the mechanism of drug action.

Computational strategies towards developing novel SARS-CoV-2 Mpro inhibitors against COVID-19.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains to be a serious threat due to the lack of a specific therapeutic agent. Computational methods are particularly suitable for rapidly fight against SARS-CoV-2. This present research aims to systematically explore the interaction mechanism of a series of novel bicycloproline-containing SARS-CoV-2 Mpro inhibitors through integrated computational approaches. We designed six structurally modified novel SARS-CoV-2 Mpro inhibitors based on the QSAR study. The four designed compounds with higher docking scores were further explored through molecular docking, molecular dynamics (MD) simulations, free energy calculations, and residual energy contributions estimated by the MM-PBSA approach, with comparison to compound 23(PDB entry 7D3I). This research not only provides robust QSAR models as valuable screening tools for the development of anti-COVID-19 drugs, but also proposes the newly designed SARS-CoV-2 Mpro inhibitors with nanomolar activities that can be potentially used for further characterization to treat SARS-CoV-2 virus.

MiR-146a Negatively Regulates Aspergillus fumigatus-Induced TNF-α and IL-6 Secretion in THP-1 Macrophages.

Aspergillus fumigatu (A. fumigatus) is one of the most common important fungal pathogens that cause life-threatening infectious disease in immunocompromised individuals. However, the host immune response against this pathogenic mold is not fully understood. MicroRNAs (miRNAs) play essential roles in regulating innate immunity. Thus, we investigated the function of miR-146a in inflammatory responses in macrophages after A. fumigatus stimulation in this study. We found that TNF-α and IL-6 were increased in THP-1 macrophage-like cells treated with A. fumigatus at both the mRNA and protein levels. The interaction between THP-1 macrophage-like cells and A. fumigatus resulted in a long-lasting increase in miR-146a expression dependent on p38 MAPK and NF-κB signaling. In A. fumigatus-challenged THP-1 macrophage-like cells, overexpression of miR-146a by miR-146a mimics decreased TNF-α and IL-6 production, whereas downregulation of miR-146a by anti-miR-146a significantly enhanced the level of TNF-α and IL-6. Our study demonstrates that the crosstalk between miR-146a and the inflammation-regulating p38 MAPK and NF-κB pathways might be a fine-tuning mechanism in the modulation of the inflammatory response in macrophages infected with A. fumigatus. Our findings illuminate the crucial role of miR-146a in the pathogenesis of human diseases associated with A. fumigatus infection.

Structural modification of 4, 5-dihydro-[1, 2, 4] triazolo [4, 3-f] pteridine derivatives as BRD4 inhibitors using 2D/3D-QSAR and molecular docking analysis.

Cancer treatment continues to be one of the most serious public health issues in the world. The overexpression of BRD4 protein has led to a series of malignant tumors, hence the development of small molecule BRD4 protease inhibitors has always been a hot spot in the field of medical research. In this study, a series of 4,5-dihydro-[1, 2, 4] triazolo [4, 3-f] pteridine derivatives were used to establish 3D/2D-QSAR models and to discuss the relationship between inhibitor structure and activity. Four ideal models were established, including the comparative molecular field analysis (CoMFA: [Formula: see text] = 0.574, [Formula: see text] = 0.947) model, comparative molecular similarity index analysis (CoMSIA: [Formula: see text]= 0.622, [Formula: see text] = 0.916) model, topomer CoMFA ([Formula: see text] = 0.691, [Formula: see text]= 0.912) model and hologram quantitative structure-activity relationship (HQSAR: [Formula: see text]= 0.759, [Formula: see text] = 0.963) model. They show quite good external predictive power for the test set, with [Formula: see text] values of 0.602, 0.624, 0.671 and 0.750, respectively. In addition, the contour and color code map given by the 2D/3D-QSAR model with the results of molecular docking analyzed to chalk up modification methods for improving inhibitory activity, which was verified by designing novel compounds. The analysis results are helpful to promote the modification of the inhibitor framework and to provide a reference for the construction of new and promising BRD4 inhibitor compounds.