In silico pharmacology最新文献

{"title":"Investigation of therapeutic potential of the Il24-p20 fusion protein against breast cancer: an in-silico approach.","authors":"Shahnila Qureshi, Nadeem Ahmed, Hafiz Muhammad Rehman, Muhammad Imran Amirzada, Fiza Saleem, Kainat Waheed, Afeefa Chaudhry, Iram Kafait, Muhammad Akram, Hamid Bashir","doi":"10.1007/s40203-024-00252-x","DOIUrl":"https://doi.org/10.1007/s40203-024-00252-x","url":null,"abstract":"<p><p>Targeted delivery of therapeutic anticancer chimeric molecules enhances drug efficacy. Numerous studies have focused on developing novel treatments by employing cytokines, particularly interleukins, to inhibit the growth of cancer cells. In the present study, we fused interleukin 24 with the tumor-targeting peptide P20 through a rigid linker to selectively target cancer cells. The secondary structure, tertiary structure, and physicochemical characteristics of the constructed chimeric IL-24-P20 protein were predicted by using bioinformatics tools. In-silico analysis revealed that the fusion construct has a basic nature with 175 amino acids and a molecular weight of 20 kDa. By using the Rampage and ERRAT2 servers, the validity and quality of the fusion protein were evaluated. The results indicated that 93% of the chimeric proteins contained 90.1% of the residues in the favoured region, resulting in a reliable structure. Finally, docking and simulation studies were conducted via ClusPro and Desmond Schrödinger, respectively. Our results indicate that the constructed fusion protein exhibits excellent quality, interaction capabilities, validity, and stability. These findings suggest that the fusion protein is a promising candidate for targeted cancer therapy.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"84"},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11408464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142304819","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":"Anticipatory in silico vaccine designing based on specific antigenic epitopes from <i>Streptococcus mutans</i> against diabetic pathogenesis.","authors":"Gopinath Murugan, Gugan Kothandan, Rajashree Padmanaban","doi":"10.1007/s40203-024-00260-x","DOIUrl":"10.1007/s40203-024-00260-x","url":null,"abstract":"<p><p>The metabolic disorder Type 2 Diabetes Mellitus (T2DM) is characterized by hyperglycaemia, causing increased mortality and healthcare burden globally. Recent studies emphasize the impact of metabolites in the gut microbiome on T2DM pathogenesis. One such microbial metabolite, imidazole propionate (Imp) derived from histidine metabolism, is shown to interfere with insulin signalling and other key metabolic processes. The key enzyme urocanate reductase (UrdA) is involved in ImP production. Hence, we propose to develop a novel therapeutic vaccine against the gut microbe producing Imp based on UrdA as a target for treating T2DM using immunoinformatics approach. Antigenic, non-allergic, non-toxic, and immunogenic B cell and T cell potential epitopes were predicted using immunoinformatics servers and tools. These epitopes were adjoined using linker sequences, and to increase immunogenicity, adjuvants were added at the N-terminal end of the final vaccine construct. Further, to confirm the vaccine's safety, antigenic and non-allergic characteristics of the developed vaccine construct were assessed. The tertiary structure of the UrdA vaccine sequence was predicted using molecular modelling tools. A molecular docking study was utilized to understand the vaccine construct interaction with immune receptors, followed by molecular dynamics simulation and binding free energy calculations to assess stability of the complex. In silico cloning techniques were employed to evaluate the expression and translation effectiveness of the developed vaccine in pET vector. In conclusion, this study developed an in silico epitope-based vaccine construct as a novel adjunct therapeutic for T2DM.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"86"},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142304815","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":"Discovery, lead identification and exploration of potential oxadiazole derivatives in targeting STAT3 as anti-cancer agents.","authors":"Vivek Panwar, Sounok SenGupta, Saroj Kumar, Praveen P Singh, Arun Kumar, Shavkatjon Azizov, Manoj K Gupta, Deepak Kumar","doi":"10.1007/s40203-024-00261-w","DOIUrl":"https://doi.org/10.1007/s40203-024-00261-w","url":null,"abstract":"<p><p>Oxadiazoles an important heterocyclic scaffold of medicinal importance in the field of drug discovery. In the study, a library of oxadiazole based compounds was selected for screening against STAT-3 as anti-cancer target. STAT3 is a potential target of interest in cancer therapy. A total of 544 screened library of compounds was subjected to molecular docking against STAT-3 (6NJS and 6NQU). The compounds with good dock score and binding interations were further subjected to in-silico ADME analysis followed by toxicity estimation. A total of 141 hits were selected against 6NJS and 50 hits against 6NQU and further screened for kinetic properties and drug likeliness. The compounds were screened on the basis of physico-chemical properties, solubility, gastrointestinal absorption, BBB permeability, synthetic accessibility, Lipinski and other violations. Best compounds obtained after ADME analysis were further subjected for toxicity analysis. Carcinogenecity, mutagenicity, Ames and other important parameters were considered for toxicity based screening. The best leads thus obtained (compound 114 and 40) were further subjected to molecular dynamics against the respective target proteins. MD simulations were run to access the stability of C-114 and C-40 along with the dynamic behaviour of both complexes for about 100 ns and shows good stability with the proteins.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"83"},"PeriodicalIF":0.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11401806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142304816","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 silico analysis reveals α-amylase inhibitory potential of Taraxerol (<i>Coccinia indica</i>) and Epoxywithanolide-1 (<i>Withania coagulans</i>): a possible way to control postprandial hyperglycemia-induced endothelial dysfunction and cardiovascular events.","authors":"Lokesh Ravi, Venkatesh Sadhana, Pratishtha Jain, Shree Kumari Godidhar Raghuram, Mohanasrinivasan Vaithilingam, Reji Manjunathan, Ajith Kumar Krishnan, Mookkandi Palsamy Kesavan","doi":"10.1007/s40203-024-00257-6","DOIUrl":"https://doi.org/10.1007/s40203-024-00257-6","url":null,"abstract":"<p><p>Postprandial hyperglycemia (PPG) exacerbates endothelial dysfunction and impairs vascular function in diabetes as well in healthy people. Though synthetic drugs are available to regulate PPG, the severe gastrointestinal side effects of those medications have prompted the search for alternative treatments. Recently, some phytochemicals captured the attention because of their inhibitory effects on α-amylase to control diabetes. The aim of this study was to investigate and identify potential alpha-amylase inhibitors in <i>C. indica</i> and <i>W. coagulans</i>. This study also aims to understand one of the possible mechanisms of action of plants for their anti-diabetic activity. A total of 36 phytochemical ligands were subjected for protein-ligand docking analysis. Among the phytochemicals, Taraxerol and Epoxywithanolide-I demonstrated significant binding free energy of - 10.2 kcal/mol and - 11.9 kcal/mol respectively, which was higher than the reference acarbose with - 8.6 kcal/mol. These molecules were subjected for molecular dynamics simulation (MDS) analysis with alpha-amylase protein for a duration of 150 ns. Among the three complexes, Taraxerol and Epoxywithanolide-I complexes demonstrates strong potential as inhibitors of the target protein. MDS results were analyzed via root mean square deviation (RMSD), fluctuation of residues, potential energy, radii of gyration and solvent access surface area analysis. Taraxerol demonstrated a significantly low potential energy of - 1,924,605.25 kJ/mol, and Epoxywithanolide-I demonstrated - 1,964,113.3 kJ/mol of potential energy. RMSD plot shows that Epoxywithanolide-I has much higher stability than the other MDS complexes. Drugability and toxicity studies show that the test ligands are demonstrating strong potential as drug like molecules. The results of the study conclude that, Taraxerol of <i>C. indica</i> and Epoxywithanolide-I of <i>W. coagulans</i> are strong inhibitors of alpha-amylase enzyme and that, this is one of the possible mechanisms of action of the plants for their reported anti-diabetic activities. Further <i>in-vitro</i> analysis is in demand to prove the observed results.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"82"},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11383901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142304817","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":"Preclinical pharmacology and pharmacokinetics of curcumin tagged cilostazol nanodispersion for the management of diabetic nephropathy in wister rat model.","authors":"Aruna Rawat, Samrat Chauhan, Monika, Rahul Pratap Singh, Sumeet Gupta, Vikas Jhawat","doi":"10.1007/s40203-024-00256-7","DOIUrl":"10.1007/s40203-024-00256-7","url":null,"abstract":"<p><p>To evaluate the therapeutic potential of curcumin tagged cilostazol solid nano dispersion in wistar rat streptozotocin-nicotinamide-induced diabetic nephropathy. Cilostazol (CLT), a Phosphodiesterase (PDE) inhibitor has an inhibitory effect on reactive oxygen species (ROS), and Curcumin (Cur), an antioxidant, and anti-inflammatory, are water-soluble. Solid Nano dispersions were developed using the \"Box-Behnken Design\" and emulsion solvent evaporation procedure to improve the solubility and bioavailability. Streptozotocin (SPZ) and Nicotinamide (NA) caused diabetes in Wistar rats. DN developed 30-45 days after disease induction. All rat groups underwent histological, biochemical and pharmacokinetic evaluation. The optimized batch of Cilostazol Loaded Novel Curcumin Tagged Solid Nanodispersion (CLT-15 SND) estimated renal, lipid, and cytokine profiles better than the conventional batch. CLT-15 SND, given orally to diabetic rats for 45 days, significantly lowered fasting BGL and IL-6 levels and improved lipid and kidney-profile markers and body weight compared to plain Cilostazol Loaded Solid Nanodispersion (CLT-15 WC SND). CLT-15 SND treatment groups showed decreased blood glucose by 3.38 and 9.71 percent, increased body weight by 2.81 and 5.27 percent, improved Interleukin-6 (IL-6) by 21.36 and 18.36 percent, improved urine albumin levels by 5.67 and 14.19 percent and creatinine levels by 3.125 and 37.5 percent, improved serum urea by 30.48 percent, increased serum albumin by 2.59 and 11.18 percent, and decreased creatinine and 5.03 and 8.12 percent, respectively as compared to CLT-15 WC and MP treatment animal groups. CLT and Cur reduced IL-6, kidney, and lipid markers, demonstrating their renoprotective and pancreas-protective effects. CLT and Cur's inhibition may be the mechanism.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"81"},"PeriodicalIF":0.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134896","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":"Exploring the therapeutic potential of prolinamides as multi-targeted agents for Alzheimer's disease treatment: molecular docking and molecular dynamic simulation studies.","authors":"Samuel O Olalekan, Vincent A Obakachi, Abosede A Badeji, Oyesolape B Akinsipo Oyelaja, Oluwole Familoni, Olayinka T Asekun, Segun D Oladipo, Adejoke D Osinubi","doi":"10.1007/s40203-024-00250-z","DOIUrl":"10.1007/s40203-024-00250-z","url":null,"abstract":"<p><p>Alzheimer's disease (AD) presents a significant global health challenge, with its prevalence expected to rise sharply in the coming years. Despite extensive research, effective treatments addressing the multifaceted pathophysiology of AD remain elusive. This study investigates the therapeutic potential of twenty-seven prolinamides (P1 - P27), with the focus on their interactions with key proteins implicated in AD pathogenesis. Four of the compounds, namely; 10-((4-nitrophenyl)prolyl)-10 H-phenothiazine (P14), 2-((4-nitrophenyl)prolyl)isoindoline (P19), 1-(4-formylphenyl)-<i>N</i>-(p-tolyl)pyrrolidine-2-carboxamide (P22), and <i>N</i>,1-bis(4-nitrophenyl)pyrrolidine-2-carboxamide (P27) showed promising potential as Alzheimer's drug. In-silico approaches including molecular docking, molecular dynamic (MD) simulation, post md study, physicochemical and drug-likeness parameters were employed to ascertain the potential of these compounds as inhibitors of certain proteins implicated in the pathophysiology of Alzheimer's disease. Molecular docking and dynamics simulations demonstrated that P14, P19, P22 and P27 exhibited promising binding affinities towards crucial AD-associated proteins, including Beta-Secretase 1 (BACE1), Butyrylcholinesterase (BuChE), and Tau-tubulin kinase 2 (TTBK2). Structural stability analyses revealed that prolinamides, particularly P22 and P27 for BACE1 and P14 and P19 for BuChE, exhibited greater stability than their reference ligands, indicated by lower RMSD, RoG, and RMSF values. For BuChE, Rivastigmine had a docking score of -7.0 kcal/mol, a binding free energy (ΔG_bind) of -22.19 ± 2.44 kcal/mol, RMSD of 1.361 ± 0.162 Å, RMSF of 9.357 ± 3.212 Å, and RoG of 22.919 ± 0.064 Å, whereas P19 exhibited a superior docking score of -10.3 kcal/mol, a significantly better ΔG_bind of -33.74 ± 2.84 kcal/mol, RMSD of 1.347 ± 0.132 Å, RMSF of 8.164 ± 2.748 Å, and RoG of 22.868 ± 0.070 Å. Physicochemical and pharmacokinetic assessments affirmed the drug-likeness and bioavailability of P19 notably capable of penetrating the blood-brain barrier. Compounds P19 and P22, emerged as multi-targeted ligands, offering the potential for simultaneous modulation of multiple AD-related pathways. These findings highlight the possibilities of these compounds to be explored as novel therapeutic agents for AD. They also highlight the need for further experimental validation to confirm their efficacy and safety profiles, advancing them toward clinical application in AD management.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00250-z.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"80"},"PeriodicalIF":0.0,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11365881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121435","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":"Pharmacophore mapping, 3D QSAR, molecular docking, and ADME prediction studies of novel Benzothiazinone derivatives.","authors":"Jahaan Shaikh, Salman Patel, Afzal Nagani, Moksh Shah, Siddik Ugharatdar, Ashish Patel, Drashti Shah, Dharti Patel","doi":"10.1007/s40203-024-00255-8","DOIUrl":"10.1007/s40203-024-00255-8","url":null,"abstract":"<p><p>In the quest to combat tuberculosis, DprE1, a challenging target for novel anti-tubercular agents due to its small size and membrane location, has been a focus of research. DprE1 catalyzes the transformation of DPR into Ketoribose DPX, with Benzothiazinone emerging as a potent pharmacophore for inhibiting DprE1. Clinical trial drugs such as BTZ043, BTZ038, PBTZ169, and TMC-207 have shown promising results as DprE1 inhibitors. This study employed pharmacophore mapping of Pyrazolopyridine, Dinitrobenzamide, and Benzothiazinone derivatives to identify crucial features for eliciting a biological response. Benzothiazinone (Ligand code: 73) emerged as a reference ligand with a fitness score of 3.000. ROC analysis validated the pharmacophore with an excellent score of 0.71. To build a 3D QSAR model, a series of Benzothiazinone congeneric derivatives were explored. The model exhibited strong performance, with a standard deviation of 0.1531, a correlation coefficient for the training set (R²) value of 0.9754, and a correlation coefficient for test set Q² value of 0.7632, indicating robust predictive capabilities. Contour maps guided the design of novel benzothiazinone derivatives, emphasizing steric, electrostatic, hydrophobic, H-bond acceptor, and H-bond donor groups for structure-activity relationships. Docking studies against PDB ID: 4NCR demonstrated favorable scores, with interactions aligning well with the in-built ligand 26 J. Docking validation via RMSD values supported the reliability of the docking results. This comprehensive approach aids in the design of novel benzothiazinone derivatives with potential anti-tubercular properties, contributing to the development of novel anti-tubercular agents which can be pivotal in the eradication of tuberculosis.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"79"},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116472","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":"Antibacterial activity of natural flavones against bovine mastitis pathogens: in vitro, SAR analysis, and computational study.","authors":"Ahlam Haj Hasan, Gagan Preet, Rishi Vachaspathy Astakala, Hanan Al-Adilah, Emmanuel Tope Oluwabusola, Rainer Ebel, Marcel Jaspars","doi":"10.1007/s40203-024-00253-w","DOIUrl":"10.1007/s40203-024-00253-w","url":null,"abstract":"<p><p>Bovine mastitis is a worldwide disease affecting dairy cattle and causes major economic losses in the dairy industry. Recently, the emergence of microbial resistance to the current antibiotics complicates the treatment protocol which necessitates antibiotic stewardship and further research to find new active compounds. Recently, phytobiotics have gained interest in being used as an alternative to antibiotics in the poultry industry as an antibiotic stewardship intervention. This study evaluated the in vitro antibacterial activity of 16 flavonoids against bovine mastitis pathogens. Two flavones: 2-(4-methoxyphenyl)chromen-4-one (<b>1</b>) and 2-(3-hydroxyphenyl)chromen-4-one (<b>4</b>) showed inhibition of the growth of <i>Klebsiella oxytoca</i> with MIC values range (25-50 µg mL^- 1) followed by a structure-activity relationship (SAR) study indicating that the presence of a hydroxyl group at C-3` or methoxy at C-4` increases the activity against <i>Klebsiella oxytoca</i> while the presence of hydroxyl group at C-7 decreases the activity. Furthermore, a structure-based drug development approach was applied using several in silico tools to understand the interactions of active flavones at the active site of the DNA gyrase protein. Compound (<b>4</b>) showed a higher docking score than quercetin (standard) which is known to have antibacterial activity by inhibiting the DNA gyrase. In addition, the structure-based pharmacophores of compound (<b>4</b>) and quercetin showed similar pharmacophoric features and interactions with DNA gyrase. Based on our findings, compounds (<b>1</b>) and (<b>4</b>) are promising for further study as potential anti-microbial phytochemicals that can have a role in controlling bovine mastitis as well as to investigate their mechanism of action further.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00253-w.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"78"},"PeriodicalIF":0.0,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057662","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":"Optimization of wet granulation process for manufacturing Rivaroxban generic immediate-release tablets using PBPK modeling and simulations.","authors":"Jailani Shiekmydeen, Tanisha, Sonam Sharma, Kishor Chakraborty, Dhanapal Chidambaram Kannaiyan, Noohu Abdulla Khan, Rajkumar Malayandi","doi":"10.1007/s40203-024-00249-6","DOIUrl":"10.1007/s40203-024-00249-6","url":null,"abstract":"<p><p>Granulation is the critical process for the pharmaceutical development of poorly water-soluble drug products. Poorly formulated products have challenges in dissolution and bioequivalence studies. Rivaroxaban (RXB) is a poorly soluble drug and has 66% fasting bioavailability at a high strength of 20 mg. Establishing the bioequivalence between test and reference products for high strength requires comparative dissolution profiles and bioequivalence. Improper granulation products and the rest of the batches failed in virtual bioequivalence. The present study provided insight into the optimization of the wet granulation process for manufacturing RXB generic immediate-release tablets using PBPK modeling and simulations. Furthermore, PBPK models are not only useful for formulation optimization but also for process optimization during pharmaceutical product development.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00249-6.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"77"},"PeriodicalIF":0.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11341787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057664","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-silico binding affinity of a phage display library screened novel peptide against various FABPs.","authors":"Harshita Shand, Soumendu Patra, Bavya Chandrasekhar, Sharvari Kulkarni, Thirumurthy Madhavan, Suvankar Ghorai","doi":"10.1007/s40203-024-00251-y","DOIUrl":"10.1007/s40203-024-00251-y","url":null,"abstract":"<p><p>In accordance to the American Heart Association (AHA), cardiovascular diseases (CVDs) are the leading cause of death around the globe, causing more than 19.1 million deaths in 2020. Heart-type fatty acid binding protein (H-FABP) is required for the metabolism of fatty acids (FA) inside cardiomyocytes is reported as a biomarker for myocardial damage. As early as one hour after an Acute myocardial infarction (AMI), H-FABP can be used to detect myocardial ischemia. Thus, H-FABP based detection can reduce the burden on the emergency department. A peptide-based detection system can provide point-of-care diagnostics for CVDs. There is a lot of research being done on peptide-based detection, and it has a lot of potential to help with unmet medical diagnostic needs. A twelve (12) amino acid peptide has been discovered using Phage Display Library Screening. The affinity of peptide with H-FABP and other FABPs has been done using molecular docking and ADMET profile has been done. Molecular docking of small peptides against the target protein can play a crucial role in recognizing peptide binding sites and poses. The docking study was done using the HDOCK server and the visualization of the docked complex was done using Pymol and UCSF chimera. The molecular simulation study of three protein-peptide complexes were done which also validated the binding affinity of peptide with the proteins. The RMSD, RMSF and radius of gyration are also analyzed. The results indicate that H-FABP shows higher level of binding interaction with the peptide having bond length ranging from 2.3 to 3.4 Å. The screened peptide is suitable for H-FABP binding and can be used for prognosis purposes in the heart ischemic conditions.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"76"},"PeriodicalIF":0.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11339228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057663","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}