Search For Targets Research Articles

Diversity in B7-H3/CD276 expression across cancer types: Exploring a dynamic novel immune checkpoint.

3133 Background: The resistance encountered in immune checkpoint blockade has persistently impaired the achievement of robust, durable antitumor immune responses in most cancer patients, prompting the search for additional immune targets. B7 homolog 3 (B7-H3)/CD276 is an emerging immune biomarker whose contrasting immune functions challenge conventional immune marker classifications, making it a compelling target. The present study aimed to characterize the expression of B7-H3/CD276 in a pan-cancer setting, analyze its co-expression patterns with potentially co-targetable immune checkpoints, and discuss implications for ongoing clinical trials. Methods: We conducted a focused analysis of B7-H3/CD276 expression in 514 cancer patients with diverse tumor histologies evaluated under the PREDICT protocol at the University of California San Diego. RNA sequencing of tissue specimens was performed, and results were used to characterize the RNA expression levels of B7-H3/CD276 and its correlation with key cancer immunity markers including PD-1, PD-L1, PD-L2, CTLA4, LAG3, BTLA, TIM3, VISTA, ADORA2A and IDO1. Results: Elevated expression levels of B7-H3/CD276 were observed in 41.6% [214/514] of the 514 tumor samples analyzed. When stratified by cancer type, the highest rates of elevated expression were found in sarcomas (58.30%, 14/24), followed by pancreatic (58.20%, 32/55) and liver and bile duct cancers (52.60%, 10/19). The independent association with pancreatic cancers was statistically significant on multivariate analysis (odds ratio 2.20, 95% confidence interval 1.09 – 4.45, p = 0.027). Ninety-three unique patterns of immune co-expression were observed among the 214 patients with high B7-H3/CD276 expression levels. Among them, the most commonly observed pattern was high expression of B7-H3/CD276 alone (26.2%, 56/214) followed by co-expression with high VISTA (7.0%, [15/214]) and high ADORA2A (5.6%, [12/214]). Of note, there was significant heterogeneity observed in the patterns of co-expression in cancer immunity markers, with 72.04% (67/93) in the cohort being unique to one patient. Conclusions: We have observed immunomic diversity in our analysis of B7-H3/CD276 expression levels across varied tumor types as well as in its co-expression patterns with other immune markers. Our findings suggest that leveraging immune profiling to build customized therapeutic regimens may be pertinent to optimizing response rates and minimizing toxicity to B7-H3/CD276 targeting therapies.

Efficient Target Search and Detection in RIS-Aided Integrated Sensing and Communications System

Efficient Target Search and Detection in RIS-Aided Integrated Sensing and Communications System

A deep analysis for New Horizons’ KBO search images

Abstract Observation datasets acquired by the Hyper Suprime-Cam (HSC) on the Subaru Telescope for NASA’s New Horizons mission target search were analyzed through a method devised by JAXA. The method makes use of Field Programmable Gate arrays and was originally used to detect fast-moving objects such as space debris or near-Earth asteroids. Here we present an application of the method to detect slow-moving Kuiper Belt Objects (KBOs) in the New Horizons target search observations. A cadence that takes continuous images of one HSC field of view for half a night fits the method well. The observations for the New Horizons Kuiper Belt Extended Mission (NH/KEM) using HSC began in 2020 May, and are ongoing. Here we show our result of the analysis of the dataset acquired from 2020 May through 2021 June that have already passed the proprietary period and are open to the public. We detected 84 KBO candidates in the 2020 June and 2021 June datasets, when the observation field was close to opposition.

Protein homeostasis maintained by HOOK1 levels promotes the tumorigenic and stemness properties of ovarian cancer cells through reticulum stress and autophagy

BackgroundOvarian cancer has a high mortality rate mainly due to its resistance to currently used therapies. This resistance has been associated with the presence of cancer stem cells (CSCs), interactions with the microenvironment, and intratumoral heterogeneity. Therefore, the search for new therapeutic targets, particularly those targeting CSCs, is important for improving patient prognosis. HOOK1 has been found to be transcriptionally altered in a substantial percentage of ovarian tumors, but its role in tumor initiation and development is still not fully understood.MethodsThe downregulation of HOOK1 was performed in ovarian cancer cell lines using CRISPR/Cas9 technology, followed by growth in vitro and in vivo assays. Subsequently, migration (Boyden chamber), cell death (Western-Blot and flow cytometry) and stemness properties (clonal heterogeneity analysis, tumorspheres assay and flow cytometry) of the downregulated cell lines were analysed. To gain insights into the specific mechanisms of action of HOOK1 in ovarian cancer, a proteomic analysis was performed, followed by Western-blot and cytotoxicity assays to confirm the results found within the mass spectrometry. Immunofluorescence staining, Western-blotting and flow cytometry were also employed to finish uncovering the role of HOOK1 in ovarian cancer.ResultsIn this study, we observed that reducing the levels of HOOK1 in ovarian cancer cells reduced in vitro growth and migration and prevented tumor formation in vivo. Furthermore, HOOK1 reduction led to a decrease in stem-like capabilities in these cells, which, however, did not seem related to the expression of genes traditionally associated with this phenotype. A proteome study, along with other analysis, showed that the downregulation of HOOK1 also induced an increase in endoplasmic reticulum stress levels in these cells. Finally, the decrease in stem-like properties observed in cells with downregulated HOOK1 could be explained by an increase in cell death in the CSC population within the culture due to endoplasmic reticulum stress by the unfolded protein response.ConclusionHOOK1 contributes to maintaining the tumorigenic and stemness properties of ovarian cancer cells by preserving protein homeostasis and could be considered an alternative therapeutic target, especially in combination with inducers of endoplasmic reticulum or proteotoxic stress such as proteasome inhibitors.

Visual and Haptic Guidance for Enhancing Target Search Performance in Dual-Task Settings

In complex environments, users frequently need to manage multiple tasks simultaneously, which poses significant challenges for user interface design. For instance, when driving, users must maintain continuous visual attention on the road ahead while also monitoring rearview mirrors and performing shoulder checks. These multitasking scenarios present substantial design challenges in effectively guiding users. To address these challenges, we focus on investigating and designing visual and haptic guidance systems to augment users’ performance. We initially propose the use of visual guidance, specifically employing a dynamic arrow as a guidance technique. Our evaluation shows that dynamic arrows significantly expedite both reaction and selection times. We further introduce and evaluate haptic feedback, which users perceive as more salient than visual guidance, leading to quicker responses when switching from primary to secondary tasks. This allows users to maintain visual attention on the primary task while simultaneously responding effectively to haptic cues. Our findings suggest that multimodal guidance, especially haptic guidance, can enhance both reaction time and user experience in dual-task environments, offering promising practical implications and guidelines for designing more user-friendly interfaces and systems.

GAGA zinc finger transcription factor searches chromatin by 1D-3D facilitated diffusion.

To elucidate how eukaryotic sequence-specific transcription factors (TFs) search for gene targets on chromatin, we used multi-color smFRET and single-particle imaging to track the diffusion of purified GAGA-Associated Factor (GAF) on DNA and nucleosomes. Monomeric GAF DNA-binding domain (DBD) bearing one zinc finger finds its cognate site by 1D or 3D diffusion on bare DNA and rapidly slides back-and-forth between naturally clustered motifs for seconds before escape. Multimeric, full-length GAF also finds clustered motifs on DNA by 1D-3D diffusion, but remains locked on target for longer periods. Nucleosome architecture effectively blocks GAF-DBD 1D-sliding into the histone core but favors retention of GAF-DBD when targeting solvent-exposed sites by 3D-diffusion. Despite the occlusive power of nucleosomes, 1D-3D facilitated diffusion enables GAF to effectively search for clustered cognate motifs in chromatin, providing a mechanism for navigation to nucleosome and nucleosome-free sites by a member of the largest TF family.

Simultaneous Search and Tracking of Non-cooperative Mobile Targets Using Multiple UAVs in Uneven Environments

Simultaneous Search and Tracking of Non-cooperative Mobile Targets Using Multiple UAVs in Uneven Environments

Algorithm for the development of a multicomponent pharmaceutical substance of plant origin with antimicrobial action: from science search to dosage form

Introduction. Despite the proven clinical efficacy of antifungal and anti-inflammatory drugs for the prevention and treatment of seborrheic dermatitis, the search for new targets and the development of new substances with a beneficial effect on the scalp microflora, with a low risk of antimicrobial resistance and adverse effects, are relevant.Aim. Development of the antimicrobial multicomponent pharmaceutical substance of plant origin in stages: from a literature search for promising substances, analysis of their composition by GC-MS, in silico evaluation of the affinity of individual components to pathogenetic targets, selection of the optimal composition of a multicomponent substance based on the results of in vitro research of antimicrobial action and the making of a medical dosage form based on it – a medicinal shampoo for the treatment of seborrheic dermatitis.Materials and methods. Objects of research: tea tree essential oil, 1,8-cineole, α-(-)-bisabolol and the multicomponent substance based on them. Methods: molecular docking (AutoDock version 4.2), prediction of pharmacological activity (Phyto4Health), TLC, GC-MS, study of antimicrobial activity in vitro.Results and discussion. Based on the results of a literature search, 3 promising substances were selected for the development of a multicomponent plant-based substance: tea tree essential oil, 1,8-cineole and α-(-)-bisabolol. Molecular docking predicted the targeted activity of the phytochemicals of tea tree essential oil, 1,8-cineole and α-(-)-bisabolol on the domains of ABC-transporters of microorganisms involved in the pathogenesis of seborrheic dermatitis and justified the possibility of use for therapy. The multicomponent substance has been developed based on tea tree essential oil, 1,8-cineole and α-(-)-bisabolol in a mass ratio of 1 : 1 : 1. The qualitative composition of the substance was assessed by TLC and GC-MS methods, and 15 terpenes were quantitatively identified in its composition with a predominance of terpinen-4-ol (16.98 %), 1,8-cineole (25.63 %) and α-(-)-bisabolol (27.67 %). The synergistic antimicrobial activity of the substance has been established against S. epidermidis, S. aureus, C. albicans and M. furfur in comparison with benzalkonium chloride, ketoconazole and climbazole. The composition of a new medical shampoo based on the investigated substance has been developed, which has a pronounced antifungal effect (more than 99.0 %) against M. furfur without visible suppression of normal microflora. For the novel substance of plant origin and medical shampoo, quality parameters were assessed in accordance with the Russian Pharmacopoeia of XIV edition.Conclusion. A substance of plant origin with synergistic and targeted antimicrobial activity has been developed. It has an interest for further study as a drug and API for new products for the treatment of seborrheic dermatitis.

CARTAR: a comprehensive web tool for identifying potential targets in chimeric antigen receptor therapies using TCGA and GTEx data.

Chimeric antigen receptor (CAR) therapy has emerged as a ground-breaking advancement in cancer treatment, harnessing the power of engineered human immune cells to target and eliminate cancer cells. The escalating interest and investment in CAR therapy in recent years emphasize its profound significance in clinical research, positioning it as a rapidly expanding frontier in the field of personalized cancer therapies. A crucial step in CAR therapy design is choosing the right target as it determines the therapy's effectiveness, safety and specificity against cancer cells, while sparing healthy tissues. Herein, we propose a suite of tools for the identification and analysis of potential CAR targets leveraging expression data from The Cancer Genome Atlas and Genotype-Tissue Expression Project, which are implemented in CARTAR website. These tools focus on pinpointing tumor-associated antigens, ensuring target selectivity and assessing specificity to avoid off-tumor toxicities and can be used to rationally designing dual CARs. In addition, candidate target expression can be explored in cancer cell lines using the expression data for the Cancer Cell Line Encyclopedia. To our best knowledge, CARTAR is the first website dedicated to the systematic search of suitable candidate targets for CAR therapy. CARTAR is publicly accessible at https://gmxenomica.github.io/CARTAR/.

#2925 PI3K/AKT/mTOR pathway regulates renal expression of Klotho

Abstract Background and Aims Renal Klotho expression decreases early in chronic kidney disease (CKD), increasing circulating FGF23 and phosphate levels. This negatively affects renal disease progression and cardiovascular complications. Preserving renal Klotho expression is of interest, but the underlying mechanisms are unclear. During early stages of CKD, kidneys activate mechanisms of hypertrophy, in which the PI3K/Akt/mTOR pathway plays a role. The main negative regulator of this pathway is PTEN, which reduces the activation of canonical insulin signaling. Kidney transplantation is the treatment of choice for patients with end-stage kidney disease. However, complications may appear after transplantation, such as allograft reaction, compromising the function and the integrity of the transplanted kidney. Different immunosuppressants are currently administered to prevent this response, such as mTOR inhibitors or calcineurin antagonists. We aimed to investigate the role of PTEN and the PI3K/AKT/mTOR pathway in kidney Klotho levels and their possible implication in CKD. Method We measured renal Klotho levels, circulating FGF23, and phosphate in mice lacking PTEN in renal proximal tubular cells (PTEC) and in HK2 cells in vitro. We also examined normal mice with models of decreased renal mass caused by uninephrectomy (UNX) and 5/6 nephrectomy (SNX). Additionally, we tested the effect of mTOR inhibition. We analyzed PTEN and Klotho expression in kidney samples from CKD patients. Furthermore, we stablished whether there are improvements in Klotho expression in patients treated with an mTOR inhibitor versus other treatments. Results We found that PTEC with downregulated PTEN exhibited decreased Klotho expression both in vitro and in vivo, accompanied by increased mTOR activity. Animals with PTEN elimination in PTEC also showed increased circulating phosphate and FGF23 levels, as well as a decrease in the fractional excretion of phosphate. These alterations were normalized by treatment with rapamycin. Normal mice with UNX or SNX exhibited increased renal IGF-1 expression and activation of the PI3K/AKT/mTOR pathway. Furthermore, these mice showed a reduction in renal Klotho expression and an increase in circulating FGF23 and phosphate. Both of these alterations were restored with rapamycin administration. In renal samples from CKD patients, we observed a positive correlation between the expression of PTEN and KLOTHO. Finally, kidney transplanted patients treated during 9 months with mTOR have an increase of 22.8% Klotho levels and patients with other treatments a 14%. Conclusion The overactivation of the PI3K/AKT/mTOR pathway in PTEC modulates Klotho levels in the kidney. Our findings represent a significant advancement in the search for new therapeutic targets to maintain and prevent reductions in renal Klotho levels, potentially benefiting kidney disease patients.

UAV Swarm Cooperative Dynamic Target Search: A MAPPO-Based Discrete Optimal Control Method

Unmanned aerial vehicles (UAVs) are commonly employed in pursuit and rescue missions, where the target’s trajectory is unknown. Traditional methods, such as evolutionary algorithms and ant colony optimization, can generate a search route in a given scenario. However, when the scene changes, the solution needs to be recalculated. In contrast, more advanced deep reinforcement learning methods can train an agent that can be directly applied to a similar task without recalculation. Nevertheless, there are several challenges when the agent learns how to search for unknown dynamic targets. In this search task, the rewards are random and sparse, which makes learning difficult. In addition, because of the need for the agent to adapt to various scenario settings, interactions required between the agent and the environment are more comparable to typical reinforcement learning tasks. These challenges increase the difficulty of training agents. To address these issues, we propose the OC-MAPPO method, which combines optimal control (OC) and Multi-Agent Proximal Policy Optimization (MAPPO) with GPU parallelization. The optimal control model provides the agent with continuous and stable rewards. Through parallelized models, the agent can interact with the environment and collect data more rapidly. Experimental results demonstrate that the proposed method can help the agent learn faster, and the algorithm demonstrated a 26.97% increase in the success rate compared to genetic algorithms.

Isolation and phenotypic characterization of cancer stem cells from metastatic oral cancer cells.

To isolate cancer stem cells (CSC) from a metastatic oral squamous cell carcinoma (OSCC) cell line and investigate their invitro and invivo phenotypic characteristics. Subpopulations with individual staining intensities for CD44 and CD326 were isolated from the OSCC cell line LN-1A by FACS: CD44Low/CD326- (CSC-M1), CD44Low/CD326High (CSC-E), and CD44High/CD326- (CSC-M2). Proliferation, clonogenic potential, adhesion, migration, epithelial-mesenchymal transition markers, and sensitivity to cisplatin and TVB-3166 were analyzed invitro. Tumor formation and metastasis were assessed by subcutaneous and orthotopic inoculations into BALB/c mice. E-cadherin levels were higher in CSC-E cells while vimentin and Slug more produced by CSC-M2 cells. CSC-M1 and CSC-M2 subpopulations showed higher proliferation, produced more colonies, and have stronger adhesion to the extracellular matrix. All cell lines established tumors; however, CSC-E and CSC-M2 formed larger masses and produced more metastases. The CSC subpopulations here described show increased cancer capabilities invitro, tumorigenic and metastatic potential invivo, and may be exploited in the search for novel therapeutic targets for OSCC.

Plant-Based HSP90 Inhibitors in Breast Cancer Models: A Systematic Review.

Breast cancer, the most invasive cancer in women globally, necessitates novel treatments due to prevailing limitations of therapeutics. Search of news anticancer targets is more necessary than ever to tackle this pathology. Heat-Shock Protein 90 (HSP90), a chaperone protein, is implicated in breast cancer pathogenesis, rendering it an appealing target. Looking for alternative approach such as Plant-based compounds and natural HSP90 inhibitors offer promising prospects for innovative therapeutic strategies. This study aims to identify plant-based compounds with anticancer effects on breast cancer models and elucidate their mechanism of action in inhibiting the HSP90 protein. A systematic review was conducted and completed in January 2024 and included in vitro, in vivo, and in silico studies that investigated the effectiveness of plant-based HSP90 inhibitors tested on breast cancer models. Eleven studies were included in the review. Six plants and 24 compounds from six different classes were identified and proved to be effective against HSP90 in breast cancer models. The studied plant extracts showed a dose- and time-dependent decrease in cell viability. Variable IC50 values showed antiproliferative effects, with the plant Tubocapsicum anomalum demonstrating the lowest value. Withanolides was the most studied class. Fennel, Trianthema portulacastrum, and Spatholobus suberectus extracts were shown to inhibit tumor growth and angiogenesis and modulate HSP90 expression as well as its cochaperone interactions in breast cancer mouse models. The identified plant extracts and compounds were proven effective against HSP90 in breast cancer models, and this inhibition showed promising effects on breast cancer biology. Collectively, these results urge the need of further studies to better understand the mechanism of action of HSP90 inhibitors using comparable methods for preclinical observations.

On the utility of ultrafast MS1-only proteomics in drug target discovery studies based on thermal proteome profiling method.

Advances in high-throughput high-resolution mass spectrometry and the development of thermal proteome profiling approach (TPP) have made it possible to accelerate a drug target search. Since its introduction in 2014, TPP quickly became a method of choice in chemical proteomics for identifying drug-to-protein interactions on a proteome-wide scale and mapping the pathways of these interactions, thus further elucidating the unknown mechanisms of action of a drug under study. However, the current TPP implementations based on tandem mass spectrometry (MS/MS), associated with employing lengthy peptide separation protocols and expensive labeling techniques for sample multiplexing, limit the scaling of this approach for the ever growing variety of drug-to-proteomes. A variety of ultrafast proteomics methods have been developed in the last couple of years. Among them, DirectMS1 provides MS/MS-free quantitative proteome-wide analysis in 5-min time scale, thus opening the way for sample-hungry applications, such as TPP. In this work, we demonstrate the first implementation of the TPP approach using the ultrafast proteome-wide analysis based on DirectMS1. Using a drug topotecan, which is a known topoisomerase I (TOP1) inhibitor, the feasibility of the method for identifying drug targets at the whole proteome level was demonstrated for an ovarian cancer cell line.

The causal relationship between serum metabolites and acne vulgaris: a Mendelian randomization study

In individuals with acne vulgaris, alterations occur in serum metabolite composition, yet the exact causal link between these metabolites and acne development remains elusive. Using genome-wide association datasets, we performed bidirectional Mendelian randomization (MR) to investigate the potential causal relationship between 309 serum metabolites and acne vulgaris. We performed sensitivity analysis to evaluate the presence of heterogeneity and pleiotropy. Forward MR analysis found 14 serum metabolites significantly associated with acne vulgaris, and reverse MR analysis found no significant association between acne vulgaris and these serum metabolites. Through validation using data from the FinnGen database of acne vulgaris studies, we found a conclusive and significant correlation between stearoylcarnitine and acne vulgaris. This provides new evidence in the search for new targets for the treatment of acne vulgaris.

Methods and clinical biomarker discovery for targeted proteomics using Olink technology.

This paper is to offer insights for designing research utilizing Olink technology to identify biomarkers and potential therapeutic targets for disease treatment. We discusses the application of Olink technology in oncology, cardiovascular, respiratory and immune-related diseases, and Outlines the advantages and limitations of Olink technology. Olink technology simplifies the search for therapeutic targets, advances proteomics research, reveals the pathogenesis of diseases, and ultimately helps patients develop precision treatments. Although proteomics technology has been rapidly developed in recent years, each method has its own disadvantages, so in the future research, more methods should be selected for combined application to verify each other.

Multi-AUV underwater static target search method based on consensus-based bundle algorithm and improved Glasius bio-inspired neural network

This research introduces a hierarchical strategy for static target searches with multi-autonomous underwater vehicles (AUVs) to optimize cumulative search rewards. The approach comprises two primary elements: task allocation and path planning. A Voronoi diagram segments regions based on peak detection via a maximum filter in the task allocation stage. Then, a consensus-based bundling algorithm ensures the load-balanced distribution of peak sub-regions across AUVs, while a dynamic cooperation mechanism allows for dynamic adjustment of task allocation, thereby increasing the system's operational flexibility. Path planning employs an improved Glasius bio-inspired neural network, leveraging analogies to convolution processes and incorporating mean pooling, multiple convolutions, and resampling. This method enhances global information propagation and optimizes path point selection through a discounted reward function evaluating adjacent nodes, thus boosting the search efficiency of individual AUVs. Simulation experiments validate the method's effectiveness and robustness in multi-AUV static target searches, demonstrating its potential to improve search efficiency.

Optimizing Search and Rescue Strategies for Deep-Sea Submersibles Using the Monte Carlo Method

Deep-sea exploration is an important field where humans challenge the limits of nature. Improving its safety and efficiency is of great significance to deep-sea scientific research and resource development. In response to this, this study established a Monte Carlo-based motion model to predict the location of the crashed submersible. To truly simulate the distress environment of the submersible, this study introduced the Monte Carlo method to randomly generate 2,000 particles to reflect the uncertainty of the initial distress location, ocean current direction, and seawater density. Finally, it was combined with a six-degree-of-freedom kinematic model to generate All possible time-varying trajectories. This study also compared the effects before and after using the corresponding equipment and found that the equipment has a good effect on reducing uncertainties. This paper expands the field focused on floating objects on the sea surface to the search for underwater targets.

Development of a new affinity maturation protocol for the construction of an internalizing anti-nucleolin antibody library

Over the last decades, monoclonal antibodies have substantially improved the treatment of several conditions. The continuous search for novel therapeutic targets and improvements in antibody’s structure, demands for a constant optimization of their development. In this regard, modulation of an antibody’s affinity to its target has been largely explored and culminated in the discovery and optimization of a variety of molecules. It involves the creation of antibody libraries and selection against the target of interest. In this work, we aimed at developing a novel protocol to be used for the affinity maturation of an antibody previously developed by our group. An antibody library was constructed using an in vivo random mutagenesis approach that, to our knowledge, has not been used before for antibody development. Then, a cell-based phage display selection protocol was designed to allow the fast and simple screening of antibody clones capable of being internalized by target cells. Next generation sequencing coupled with computer analysis provided an extensive characterization of the created library and post-selection pool, that can be used as a guide for future antibody development. With a single selection step, an enrichment in the mutated antibody library, given by a decrease in almost 50% in sequence diversity, was achieved, and structural information useful in the study of the antibody-target interaction in the future was obtained.

Estrogen-related receptor, a molecular target against lepidoptera pests

Until recently, chemical pesticides were one of the most effective means of controlling agricultural pests; therefore, the search for insecticide targets for agricultural pests has been an ongoing problem. Estrogen-related receptors (ERRs) are transcription factors that regulate cellular metabolism and energy homeostasis in animals. Silkworms are highly sensitive to chemical pesticides, making them ideal models for pesticide screening and evaluation. In this study, we detected ERR expression in key organs involved in pesticide metabolism in silkworms (Bombyx mori), including the fat body and midgut. Using ChIP-seq technology, many estrogen- related response elements were identified in the 2000-bp promoter region upstream of metabolism-related genes, almost all of which were potential ERR target genes. The ERR inhibitor, XCT-790, and the endocrine disruptor, bisphenol A, significantly inhibited expression of the ERR target genes, BmTreh-1, BmTret-1, BmPK, BmPFK, and BmHK, in the fat bodies of silkworms, resulting in pupation difficulties in silkworm larvae that ultimately lead to death. In addition, based on the clarification that the ERR can bind to XCT-790, as observed through biofilm interferometry, its three-dimensional spatial structure was predicted, and using molecular docking techniques, small-molecule compounds with a stronger affinity for the ERR were identified. In summary, utilizing the powerful metabolic regulatory function of ERR in Lepidoptera pests, the developed small molecule inhibitors of ERR can be used for future control of Lepidoptera pests.