key: cord-0074993-hqrcv3tm authors: Sivasakthi, Priya; Sabarathinam, Sarvesh; Vijayakumar, Thangavel Mahalingam title: Network pharmacology and in silico pharmacokinetic prediction of Ozanimod in the management of ulcerative colitis: A computational study date: 2022-01-19 journal: Health Sci Rep DOI: 10.1002/hsr2.473 sha: 79eb5c5c9a9a7f0b00c52c4dcafd8b264ada3587 doc_id: 74993 cord_uid: hqrcv3tm nan Inflammatory bowel disorders are non-infectious chronic inflammation of the esophageal tract (IBD). IBD is divided into two types: ulcerative colitis (UC) and Crohn's disease. The highest incidence and prevalence rates of ulcerative colitis are seen in North America and northern Europe, with incidence rates ranging from 9 to 20 cases per 100 000 person-years and prevalence rates ranging from 156 to 291 cases per 100 000 persons. 1 OZM is contraindicated in patients with previous history of cardiovascular complications. The dose and dosage of OZM is 0.23 mg by oral route (qDay) for 1 to 4 days followed by 5 to 7:0.46 mg and on eighth day titrated to 0.92 mg PO (qDay). OZM is not highly recommended in pregnant and lactating women since existing animal studies not reported with enough evidence. The in silico analysis of Ozanimod (OZM) is not yet been fully characterized. The current study was designed to investigate the pharmacokinetic profile of the OZM and its interaction potential with UC target protein. OZM is a sphingosine-1-phosphate (S1P) receptor modulator approved by FDA in March 2020 for UC. The molecular weight of OZM is 404.47, with 07 rotatable bonds and acceptable bonds. The water solubility rate was À3.154 (log mol/L), the intestinal absorption rate is 91.053% in humans, OZM is a substrate of P-glycoprotein, and CYP3A4 followed by an inhibitor of P-glycoprotein I and II, clearance 0.69 (log ml/min/kg), Minnow toxicity À0.231(log mM). 2 The estimated activity of a substance is predicted as probable activity Target Proteins between AID, UC, and OZM showed that 24 target proteins were overlapping between the two public databases 6 ( Figure 1B ). Protein-protein interaction from 24 overlapping target proteins from STRING analysis shows that 24 nodes, 123 edges, and PPI enrichment P-value was <1.0e-16. The P-value indicates that there was a significant connection between the protein and biological activity of the drug. In protein-protein interaction (PPI), the MAPK1 target exhibited the highest degree and is considered as a hub target protein 7 ( Figure 1C ). In determining binding affinities and interactions of OZM with MAPK1 in pyRx virtual screening tool, 8 The docking score for OZM G against MAPK1 was À7.7 kcal/mol. The docked compound is illustrated in Figure 1D . Due to the good binding affinity, this analysis indicated that our predicted compound might be more effective in the management of UC. The increased mortality rate is observed in geriatrics with existing complications like infection, shock, anemia, and those who require repeated surgical interventions. Clinical trials reported 01 mg of OZM is administered in both trials with placebo as a control group, there was a significant change between the control group and treatment group (Table 1) We extend our sincere thanks to all the health care professionals. No specific funding was obtained for this study. No conflicts of interest have been identified or declared by any of the authors. Conceptualization: Sarvesh Sabarathinam. Corresponding author, Vijayakumar, had full access to all of the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis. The lead author, Vijayakumar, affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained. The data that support the findings of this study are available from the corresponding author upon reasonable request. Ulcerative colitis Synthesis, in vitro antifungal evaluation and in silico study of 3-azolyl-4-chromanone phenylhydrazones Design, synthesis and ADMET prediction of bis-benzimidazole as anticancer agent In silico identification of potential inhibitors from cinnamon against main protease and spike glycoprotein of SARS CoV-2 Therapeutic use of Guggulsterone in COVID-19 induced obesity (COVIBESITY) and significant role in immunomodulatory effect A network pharmacology analysis on drug-like compounds from Ganoderma lucidum for alleviation of atherosclerosis Network pharmacology approach to decipher signaling pathways associated with target proteins of NSAIDs against COVID-19 Drug repositioning against COVID-19: a first line treatment QSPR studies on aqueous solubilities of drug-like compounds Efficacy and safety study of Ozanimod in ulcerative colitis Safety and efficacy trial of RPC1063 for moderate to severe ulcerative colitis