Medicine in Drug Discovery最新文献

{"title":"Albumin is a reliable drug-delivering molecule: Highlighting points in cancer therapy","authors":"Akmal M. Asrorov ,&nbsp;Nurkhodja Mukhamedov ,&nbsp;Muzaffar Kayumov ,&nbsp;Ansor Sh. Yashinov ,&nbsp;Ahmidin Wali ,&nbsp;Abulimiti Yili ,&nbsp;Sharafitdin Ya. Mirzaakhmedov ,&nbsp;Yongzhuo Huang","doi":"10.1016/j.medidd.2024.100186","DOIUrl":"https://doi.org/10.1016/j.medidd.2024.100186","url":null,"abstract":"<div><p>As the most abundant protein in the blood, albumin binds and transports hydrophilic, hydrophobic, and lipophilic molecules required for the growth and development of cells and tissues. Due to the surface location of charged groups and the inner hydrophobic site, it transports proteins, peptides, amino acids, fatty acids, nutrients, and other biomolecules. It is a multi-domain protein involved in various functions of the blood, including the contribution to oncotic pressure. Because of its unique sequence and structure, albumin can be efficiently utilized to develop drug delivery systems against various diseases, including cancer. As a protein, rich in both negative and positive charges on the surface, it attracts great attention in the drug delivery discipline. Inner hydrophobic sites were proven to be an efficient location for delivering hydrophobic and lipophilic drugs. Albumin binding domains, widely distributed among receptors and matricellular molecules, ease its penetration into cells. A high ratio of cysteine provides stability to the molecule and causes thiol-disulfide interactions, which play an essential role in drug release. In this work, we highlighted several points of albumin nature as a drug-carrying molecule regarding biochemical and physical properties: self-assembling, formation of covalent bonds, formation of <em>in situ</em> albumin corona, etc. Research publications were searched in the NCBI database by various keywords related to sections/subsections to review the related topic. Tens of research works have been dedicated to enhancing the therapeutic efficacy of anticancer drugs using albumin in the last two decades and contributed to clarifying the mechanistic action of albumin. We discussed its mechanisms of action in drug delivery in the first section. In another section, we reviewed the enhanced antitumor/anticancer efficacies of those fabricated DDSs in terms of albumin contribution. The results of <em>in vitro</em> and <em>in vivo</em> experiments were merged into that section consisting of subsections of DDSs of individual anticancer means. Clinical trials of three drugs were reviewed as a separate section. The approaches used to enhance the efficacy of albumin-based DDSs were reviewed in the last section. The final section is devoted to strategies that could significantly improve albumin efficacy in cancer drug delivery.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"22 ","pages":"Article 100186"},"PeriodicalIF":0.0,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000113/pdfft?md5=32645bf86f88d9d6d9d5ae5e0f58f3e4&pid=1-s2.0-S2590098624000113-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140327685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functions and inhibitors of CHK1 in cancer therapy","authors":"Kailong Jiang ,&nbsp;Minjie Deng ,&nbsp;Wenjing Du ,&nbsp;Tao Liu ,&nbsp;Jia Li ,&nbsp;Yubo Zhou","doi":"10.1016/j.medidd.2024.100185","DOIUrl":"https://doi.org/10.1016/j.medidd.2024.100185","url":null,"abstract":"<div><p>CHK1 plays a crucial role in cancer biology as it modulates cell cycle checkpoint activation and DNA repair. Furthermore, a number of other cellular functions of CHK1 are also gradually discovered. Based on these biological functions, CHK1 has been regarded as a potential target for cancer therapy, but regrettably no CHK1 inhibitors have been marketed up to now. The incorporation of effective biomarkers or combined combinations is expected to promote the development process of CHK1 inhibitors. This paper reviews the latest research progress on the functions and inhibitors of CHK1.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"22 ","pages":"Article 100185"},"PeriodicalIF":0.0,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000101/pdfft?md5=d4ae51553b195636583049ba38db534f&pid=1-s2.0-S2590098624000101-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140350979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro human colon microbiota culture model for drug research","authors":"Tomoya Shintani ,&nbsp;Daisuke Sasaki ,&nbsp;Yasushi Matsuki ,&nbsp;Akihiko Kondo","doi":"10.1016/j.medidd.2024.100184","DOIUrl":"https://doi.org/10.1016/j.medidd.2024.100184","url":null,"abstract":"<div><p>The colonic microbiota, comprising 500 species and 40 trillion bacteria, is influenced by various factors, such as diet, habits, and constitution, which impact human health and disease. This paper discusses the significance of colonic microbiota in human health and explores various <em>in vitro</em> colonic microbiota culture models to evaluate the effects of functional ingredients on gut microbiota. Traditional evaluation methods involve animal experiments and human intervention studies. However, ethical and practical challenges remain. This study introduces the Kobe University Human Intestinal Microbiota Model (KUHIMM) as an innovative <em>in vitro</em> culture system. This study details the operational methods and distinctive features of the KUHIMM, highlighting its capacity to accurately reproduce the diversity of the colonic microbiota and the metabolites in individual human donors. Various applications of the KUHIMM have been presented, ranging from the assessment of dietary fibers and probiotics to drugs and herbal medicines. The ability of the model to predict health effects and its sensitivity in evaluating different drugs make it a valuable tool for research and development. This study acknowledges its limitations, including the absence of an absorption system for metabolites, but anticipates the increasing importance of <em>in vitro</em> gut microbiota culture systems in advancing the understanding of human health and expediting the development of effective interventions.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"22 ","pages":"Article 100184"},"PeriodicalIF":0.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000095/pdfft?md5=de2157c7e450d717f928bbeab1d3ec86&pid=1-s2.0-S2590098624000095-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140134702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A complex molecular landscape to drug delivery concept for achieving precise therapy in psoriasis","authors":"Krishna Yadav ,&nbsp;Kantrol Kumar Sahu ,&nbsp;Sucheta ,&nbsp;Renu Yadav ,&nbsp;Wasim Raza ,&nbsp;Sunita Minz ,&nbsp;Manju Rawat Singh ,&nbsp;Deependra Singh ,&nbsp;Madhulika Pradhan","doi":"10.1016/j.medidd.2024.100183","DOIUrl":"https://doi.org/10.1016/j.medidd.2024.100183","url":null,"abstract":"<div><p>Psoriasis is a chronic autoimmune disorder that has a major effect on the quality of life for millions of people throughout the world. The pathogenesis of psoriasis has revealed intricate molecular networks and signaling pathways, opening new avenues for precision medicine. Psoriasis treatments include topical therapy, phototherapy, systemic therapies, and biologics, but achieving optimal outcomes is difficult. Despite advancements in understanding the causes of psoriasis and the development of various treatments, optimizing therapeutic outcomes remains challenging. Managing psoriasis poses challenges in terms of drug delivery and evaluation models. Novel drug delivery systems capable of navigating complex skin barriers and delivering therapeutics precisely to target cells are crucial for advancing treatment options. This article provides an inclusive overview of psoriasis, highlighting recent discoveries and potential therapeutic targets. The article emphasizes the importance of combining different modalities, such as synthetic and herbal agents, with biologics to improve efficacy. Nanocarriers show promise for targeted drug delivery in psoriasis, as they can encapsulate antipsoriatic drugs, biologics, and gene therapies, providing enhanced stability, improved tissue penetration, and precise cellular targeting. These advancements in drug delivery systems have the potential to revolutionize psoriasis treatment by maximizing efficacy while minimizing side effects. The article also discusses the commercial outcomes in psoriasis formulations, including patents related to treatment and ongoing clinical trials, which provide valuable insights into the evolving landscape of psoriasis therapeutics. These insights contribute to the evolving field of psoriasis therapeutics and offer hope for improved outcomes for patients suffering from psoriasis.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"22 ","pages":"Article 100183"},"PeriodicalIF":0.0,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000083/pdfft?md5=dc8eaee6cca333d71d3a446c45bd27aa&pid=1-s2.0-S2590098624000083-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140123196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experimental and computational characterization of p-Sulfocalix[4]arene mediated delivery system for morin hydrate","authors":"Sunaina Chaurasiya ,&nbsp;Raghu Solanki ,&nbsp;Mohd Athar ,&nbsp;Ashok Kumar Jangid ,&nbsp;Sunita Patel ,&nbsp;Prakash C. Jha ,&nbsp;Deep Pooja ,&nbsp;Hitesh Kulhari","doi":"10.1016/j.medidd.2024.100180","DOIUrl":"https://doi.org/10.1016/j.medidd.2024.100180","url":null,"abstract":"<div><p>Calix[n]arene is a class of macrocyclic compounds and has been investigated to improve the physicochemical properties of water insoluble molecules. In this work, a complex of morin hydrate (MH) drug was prepared using p-sulfocalix[4]arene (SC[4]A) as complexing agent to increase its water solubility, dissolution rate and stability. Solvent evaporation methanol was used to prepare the inclusion complex (MH-SC[4]A) between pure MH and SC[4]A and analysed by FTIR, NMR, UV, DLS, TEM, and DSC techniques. Concentration-dependent solubility study showed 22 folds enhancement of MH at 8 mM concentration of SC[4]A. The <em>in vitro</em> anticancer efficacy of MH against A549 cells was increased after complex formation. AO/EtBr staining study showed the more apoptosis mediated anticancer activity than native MH. Molecular geometry, stabilizing interactions, release behaviour and full-unwinding pathway of the complex were characterized by the computed Potential of Mean Force (PMF) using extended umbrella sampling. The combined computational and experimental data confirmed that our designed MH-SC[4]A complex could be utilized as a promising drug delivery carrier for hydrophobic MH.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"22 ","pages":"Article 100180"},"PeriodicalIF":0.0,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000058/pdfft?md5=673fcfeb90f34f8122e3a96ac47d884e&pid=1-s2.0-S2590098624000058-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140067369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment response and its predictors of immunosuppressive therapy in patients with severe or very severe aplastic anemia","authors":"Thanakrit Somprasertkul ,&nbsp;Weerayaporn Trirattanapikul ,&nbsp;Sittichai Khamsai ,&nbsp;Verajit Chotmongkol ,&nbsp;Kittisak Sawanyawisuth","doi":"10.1016/j.medidd.2024.100181","DOIUrl":"https://doi.org/10.1016/j.medidd.2024.100181","url":null,"abstract":"<div><p>Severe aplastic anemia (SAA) is a hematological condition with high morbidity and mortality. Treatment with immunosuppressive agents is alternative treatment if bone marrow transplant is not available. Several studies reported predictors of successful treatment in patients with SAA. However, the results are not consistent and not specific to anti-thymocyte globulin and cyclosporine. This study aimed to evaluate the predictor of response to treatment in this specific regimen. This study was a retrospective cohort study. The inclusion criteria were adult patients with SAA or very SAA who received this regimen. Clinical factors predictive of response to treatment were computed. There were 92 patients met the study criteria. Of those, 56 patients (60.87%) were in a group of response to treatment. There were nine factors in the predictive model for good response to treatment. Only body mass index was independently associated with response to treatment with an adjusted odds ratio of 1.31 (95% confidence interval of 1.04, 1.67). Age or hematological laboratory factors such as lymphocyte or neutrophil count were not significant. Low body mass index may be less likely to response to immunosuppressive treatment in patients with severe or very severe aplastic anemia.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"22 ","pages":"Article 100181"},"PeriodicalIF":0.0,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S259009862400006X/pdfft?md5=c7cc3102353ae4f94e197711f5758dd4&pid=1-s2.0-S259009862400006X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140030220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights from clinical trials: New evidence supports surgical interventions over drug therapies for atrial fibrillation","authors":"Akshat D. Modi ,&nbsp;Akriti Sharma ,&nbsp;Dharmeshkumar M. Modi","doi":"10.1016/j.medidd.2024.100182","DOIUrl":"https://doi.org/10.1016/j.medidd.2024.100182","url":null,"abstract":"<div><p>Atrial fibrillation (AF) is one of the world’s most prevalent cardiac arrhythmias. It poses a heavy burden on patients, physicians and the global healthcare system as it is one of the top leading causes of cardiovascular death. Researchers have spent numerous years conducting clinical trials to investigate the effectiveness, cost and practicality of treatment for patients suffering from AF. The primary treatment strategy for AF (acute, chronic, persistent, paroxysmal, non-valvular, nonrheumatic, and rapid) involves the use of antiarrhythmic drugs (AAD) and anticoagulant drugs (ACD) to manage heart rate and rhythm, as well as to prevent strokes. This review aims to discuss clinical trials that compared AADs (class Ia: quinidine; class Ic: flecainide, propafenone; class III: sotalol, amiodarone) and ACDs (vitamin K antagonist: warfarin; factor Xa inhibitor: apixaban, rivaroxaban; thrombin inhibitor: dabigatran) with cardiovascular surgical interventions (i.e., catheter ablation, cryoballoon ablation, ablation and DDDR pacemaker, electrical cardioversion, and left atrial appendage occlusion) to treat various types of AF in patients with a diverse history of cardiovascular diseases and medical history. This study provides a review of clinical trials on this topic and enables healthcare professionals to determine the best-suited treatment for their patients.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"22 ","pages":"Article 100182"},"PeriodicalIF":0.0,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000071/pdfft?md5=5469dfbaebe3790d3ff06cec0bea85b0&pid=1-s2.0-S2590098624000071-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140014024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation and characterization of multi-target nanoparticles for co-drug delivery","authors":"Farnaz Ahmadi-Nouraldinvand ,&nbsp;Shima Bourang ,&nbsp;Solmaz Azizi ,&nbsp;Mohsen Noori ,&nbsp;Mehran Noruzpour ,&nbsp;Hashem Yaghoubi","doi":"10.1016/j.medidd.2024.100177","DOIUrl":"https://doi.org/10.1016/j.medidd.2024.100177","url":null,"abstract":"<div><p>Self-assembly of various amphipathic copolymers is a simple method that allows the preparation of complex nanoparticles with several useful properties. Therefore, the aim of this research was to develop nanoparticles with better biocompatibility, biodegradability, and prolonged circulation time in the bloodstream to deliver drugs and genes into breast cancer tissues in a controlled and targeted manner. In this study, the copolymers PLA-chitosan- PEG -folic acid (COPA), PLA-chitosan- PEG -glucose (COPB), COPA &amp; COPB (COPAB) and chitosan- PLA-PEG FA /Glu/VEGF/siRNA/PTX (NPsAB/siRNA/Paclitaxel) were synthesized, to control the release of paclitaxel (PTX) and siRNA and the circulation time of nanoparticles in blood. This was confirmed by ¹H NMR and FTIR spectroscopy. The particle size, zeta potential and morphology of NPsAB /siRNA/PTX were studied by DLS and TEM, respectively. The results showed that the NPsAB/siRNA/PTX had spherical morphology with particle size and zeta potential about 200 nm and −7.8 mV, respectively. In vitro cytotoxicity assay results showed that the nanoparticles had good biocompatibility and low toxicity. Also demonstrated that NPsAB in the serum medium improved the efficiency of drug and siRNA delivery more than two-fold compared to COPA, COPB, and COPAB nanoparticles. Due to results the release pattern of siRNA and PTX from NPsAB nanoparticles under an acidic environment was significantly higher than that of their release rate in a neutral medium. Therefore, due to the acidity of tumor tissue, this property of NPsAB nanoparticles seems to be useful in the treatment of cancer.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"21 ","pages":"Article 100177"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000022/pdfft?md5=a8afc8c94e0691a696c4a49e30a460e6&pid=1-s2.0-S2590098624000022-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139699878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The immunological activities and transcriptome analysis of a potent small-molecule immunomodulator","authors":"Yasser Tabana ,&nbsp;Shima Shahbaz ,&nbsp;Dinesh Babu ,&nbsp;Marawan Ahmed ,&nbsp;Tae Chul Moon ,&nbsp;Frederick G. West ,&nbsp;Richard Fahlman ,&nbsp;Arno G. Siraki ,&nbsp;Shokrollah Elahi ,&nbsp;Khaled Barakat","doi":"10.1016/j.medidd.2024.100178","DOIUrl":"https://doi.org/10.1016/j.medidd.2024.100178","url":null,"abstract":"<div><p>The use of small molecules in immunotherapy is a promising and rapidly growing field with the potential to revolutionize the way we treat a wide range of immunological diseases. The success stories of using small molecules in immunotherapy have been highlighted with many drugs, such as checkpoint inhibitors, which have achieved significant success in treating several types of tumors. However, despite this success, the development of small molecules for immunotherapy is still in its infancy, and there are many challenges that remain to be addressed. In a recent study, our laboratory reported the immunostimulatory effect of a small molecule (Compound A) (A). In this paper, we studied a derivative of this molecule (Compound B) (<span>Fig. 1</span>B). and analysed its physiochemical properties, immunological activities, and transcriptome profiling. Compound B exhibited acceptable metabolic stability and no toxicity against PBMCs. We also demonstrated that Compound B was capable of modulating the immune system by inducing pro-inflammatory cytokines and promoting T-cell proliferation. RNAseq results showed that Compound B was able to significantly upregulate genes involved in stimulating the immune response pathways. Our findings suggest that Compound B may serve as a promising therapeutic agent to modulate the immune system. The identification and validation of the molecular targets responsible for its immunological activities are underway.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"21 ","pages":"Article 100178"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000034/pdfft?md5=eeea728aad91880605a126d378551ea8&pid=1-s2.0-S2590098624000034-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139675288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revealing key structural features for developing new agonists targeting δ opioid receptor: Combined machine learning and molecular modeling perspective","authors":"Zeynab Fakhar ,&nbsp;Ali Hosseinpouran ,&nbsp;Orde Q. Munro ,&nbsp;Sorena Sarmadi ,&nbsp;Sajjad Gharaghani","doi":"10.1016/j.medidd.2024.100176","DOIUrl":"10.1016/j.medidd.2024.100176","url":null,"abstract":"<div><p>Despite being the most widely prescribed and misused type of medication, opioids continue to function as robust pain relief agents; however, overdosing is a significant cause of fatalities among opioid users. The δ-opioid receptor (DOR) has immense promise in treating long-term pain by producing anxiolytic and antidepressant-like outcomes. Although DOR agonists play a crucial role, their clinical implementation is restricted because of the probable manifestation of severe, life-threatening complications. A Python-based machine learning approach was employed to develop a quantitative structure–activity relationship (QSAR) model in this study. To address this, 4217 compounds and their associated biological inhibition activities were retrieved from the gpcrdb database. The K-best features selection method revealed three key structural features such as SLOGPVSA2, Chi6ch, and S17 contributed significantly to the best model performance. Statistical analysis, K-fold cross-validation, applicability domain analysis, and external validation using 38 unseen FDA-approved drug data confirmed the robustness of the predictive model. A molecular docking study in along with Ligand–Receptor Contact Fingerprints (LRCFs) using the essential chemical interactions described for analog ligands releaved the key contact interactions of Asp 128, Tyr 129, Met 132, Trp 274, Ile 277, and Tyr 308 residues in the total binding affinities upon complexation. Our combinatorial study using regression QSAR and ligand–receptor Contact, analysis could serve in the design of more rational compounds for drug discovery targeting DOR.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"21 ","pages":"Article 100176"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000010/pdfft?md5=dcc745d04bc41e8a714b7b19587b9f57&pid=1-s2.0-S2590098624000010-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139538669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}