An evaluation of the expression and predictive significance of the MDM2 gene in brain lower-grade glioma (LGG) cancer was carried out using onco-informatics pipelines. Several transcriptome servers were used to measure the differential expression of the targeted MDM2 gene and search mutations and copy number variations. GENT2, Gene Expression Profiling Interactive Analysis, Onco-Lnc, and PrognoScan were used to figure out the survival rate of LGG cancer patients. The protein–protein interaction networks between MDM2 gene and its co-expressed genes were constructed by Gene-MANIA tool. Identified bioactive phytochemicals were evaluated through molecular docking using Schrödinger Suite Software, with the MDM2 (PDB ID: 1RV1) target. Protein–ligand interactions were observed with key residues of the macromolecular target. A molecular dynamics simulation of the novel bioactive compounds with the targeted protein was performed. Phytochemicals targeting MDM2 protein, such as Taxifolin and (-)-Epicatechin, have been shown with more highly stable results as compared to the control drug, and hence, concluded that phytochemicals with bioactive potential might be alternative therapeutic options for the management of LGG patients. Our once informatics-based designed pipeline has indicated that the MDM2 gene may have been a predictive biomarker for LGG cancer and selected phytochemicals possessed outstanding interaction results within the macromolecular target’s active site after utilizing in silico approaches. In vitro and in vivo experiments are recommended to confirm these outcomes.

Background: ATP-binding cassette Super-family G member 2 protein is an active ATPbinding cassette transporter with the potential to combat cancer stem cells.Objective: Due to the lack of potential ATP-binding cassette Super-family G member 2 inhibitors, we screened natural inhibitors, which could be a safe source to control multidrug resistance by blocking the regulation of ATP-binding cassette Super-family G member 2 protein.Methods: Three-dimensional structure of ATP-binding cassette Super-family G member 2 protein downloaded from the protein databank and chemical structures of 166 selected compounds of the training dataset were retrieved from PubChem. Drug-likeness and docking analysis was conducted to shortlist the dataset for pharmacophore generation. LigandScout 4.1.5 used for pharmacophorebased screening of Zbc library of ZINC database and Autodock Vina were utilized for molecular docking against the predicted active pocket of the target protein to evaluate the potential association of protein and ligands. The physiochemical properties of novel compounds were calculated by admetSAR respectively.Results: Through pharmacophore-based screening, ZINC4098704 (Rhein) was identified as a lead compound which demonstrates the least binding energy (-8.5) and the highest binding affinity with the target protein and showed optimal physiochemical profile. This compound is highly recommended for a laboratory test to confirm its activity as an ATP-binding cassette Super-family G member 2 inhibitors.Conclusion: Our computer-based study systematically selected natural lead compounds, which could be effective in inhibiting ATP-binding cassette Super-family G member 2 and may help reverse the effect of multidrug resistance to increase the effectiveness of chemotherapy in cancer treatment.

Lepidoptera is the second most diverse insect order outnumbered only by the Coeleptera. Acetylcholinesterase (AChE) is the major target site for insecticides. Extensive use of insecticides, to inhibit the function of this enzyme, have resulted in the development of insecticide resistance. Complete knowledge of the target proteins is very important to know the cause of resistance. Computational annotation of insect acetylcholinesterase can be helpful for the characterization of this important protein. Acetylcholinesterase of fourteen lepidopteran insect pest species was annotated by using different bioinformatics tools. AChE in all the species was hydrophilic and thermostable. All the species showed lower values for instability index except L. orbonalis, S. exigua and T. absoluta. Highest percentage of Arg, Asp, Asn, Gln and Cys were recorded in P. rapae. High percentage of Cys and Gln might be reason for insecticide resistance development in P. rapae. Phylogenetic analysis revealed the AChE in T. absoluta, L. orbonalis and S. exigua are closely related and emerged from same primary branch. Three functional motifs were predicted in eleven species while only two were found in L. orbonalis, S. exigua and T. absoluta. AChE in eleven species followed secretory pathway and have signal peptides. No signal peptides were predicted for S. exigua, L. orbonalis and T. absoluta and follow non secretory pathway. Arginine methylation and cysteine palmotylation was found in all species except S. exigua, L. orbonalis and T. absoluta. Glycosylphosphatidylinositol (GPI) anchor was predicted in only nine species.

Sumoylation is the Post-translational modification gaining most of the research interest recently. Sumoylation is involved in various crucial functions of the cell such as regulation of cell cycle, DNA damage repair, apoptosis, etc. Oncology is advancing in radiotherapy, targeted chemotherapy, various forms of immunotherapy and targeted gene therapy. Researches are being conducted to prove its connotation with a variety of cancers and inhibitors are being developed to obstruct the fatal effect caused by misbalance of the SUMO-catalytic cycle. It has been shown that up-regulation of certain enzymes of Sumoylation correlates with cancer incidence in most of the cases. However, in some cases, down-regulation also associates with cancer invasion such as underexpression of UBC9 in initial stage breast cancer. This can aid in future study, treatment, and diagnosis of a variety of cancers including breast cancer, prostate cancer, lung adenocarcinoma, melanoma, multiple myeloma, etc. Various mechanistic assays are being developed and used to identify potential inhibitors against the dysregulated proteins of Sumoylation. This review summarizes the normal roles of the enzymes involved in the SUMOcatalytic cycle, their misbalanced regulation leading to tumorigenesis and nearly all the potent inhibitors identified to date, while after detailed studied it was observed that ML-792 could be a promising inhibitor in treating cancers by inhibiting Sumoylation enzymes.