Identification of potential bioactive phytochemicals for the inhibition of platelet-derived growth factor receptor β: a structure-based approach for cancer therapy.

Platelet-derived growth factor receptor beta (PDGFRβ) belongs to the receptor tyrosine kinase (RTK) protein family and is implicated in several disorders such as hematopoietic, glial, and soft-tissue cancer, non-cancerous disorders, including skeletal defects, brain calcification, and vascular anomalies. The research on small molecule inhibitors targeting PDGFRβ in cancer treatment has seen promising developments, but significant gaps remain. PDGFRβ, receptor tyrosine kinase, is overexpressed in various cancers and plays an important role in tumor progression, making it a potential therapeutic target.

Exploring the promising potential of noscapine for cancer and neurodegenerative disease therapy through inhibition of integrin-linked kinase-1.

Integrin-linked kinase (ILK), a β1-integrin cytoplasmic domain interacting protein, supports multi-protein complex formation. ILK-1 is involved in neurodegenerative diseases by promoting neuro-inflammation. On the other hand, its overexpression induces epithelial-mesenchymal transition (EMT), which is a major hallmark of cancer and activates various factors associated with a tumorigenic phenotype.

Identification of High-Affinity Inhibitors of TANK-Binding Kinase 1 (TBK1): A Promising Frontier for Controlling Inflammatory Signaling in Cancer.

Background: TANK-binding kinase 1 (TBK1) is an important serine/threonine kinase involved in inflammatory signaling pathways, influencing cellular processes such as proliferation, programmed cell death, autophagy, and immune response regulation. Dysregulation of TBK1 has been linked to cancer progression and neurodegenerative disorders, making it an attractive target for therapeutic development. This study aimed to identify potential TBK1 inhibitors using a structure-based virtual screening approach.

Investigating the role of thymol as a promising inhibitor of pyruvate dehydrogenase kinase 3 for targeted cancer therapy.

Protein kinases have emerged as major contributors to various diseases. They are currently exploited as a potential target in drug discovery because they play crucial roles in cell signaling, growth, and regulation. Their dysregulation is associated with inflammatory disorders, cancer, and neurodegenerative diseases.

An integrated docking and molecular dynamics simulation approach to discover potential inhibitors of activin receptor-like kinase 1.

Activin receptor-like kinase 1 (ALK1) is a transmembrane receptor involved in crucial signaling pathways associated with angiogenesis and vascular development. Inhibition of ALK1 signaling has emerged as a promising therapeutic strategy for various angiogenesis-related diseases, including cancer and hereditary hemorrhagic telangiectasia. This study aimed to investigate the potential of phytoconstituents as inhibitors of ALK1 using a combined approach of virtual screening and molecular dynamics (MDs) simulations.

Exploring the potential of phytochemicals as inhibitors of 3'-phosphoadenosine 5'-phosphosulfate synthase 1 targeting cancer therapy.

3'-phosphoadenosine 5'-phosphosulfate synthase 1 (PAPSS1) is an enzyme that critically synthesises the biologically active form of sulfate (PAPS) for all sulfation reactions. The discovery of PAPSS1 as a possible drug target for cancer therapy, specifically in non-small cell lung cancer, has prompted us to investigate potential small-molecule inhibitors of PAPSS1. Here, a structure-based virtual screening method was used to search for phytochemicals in the IMPPAT database to find potential inhibitors of PAPSS1.

Discovering Tuberosin and Villosol as Potent and Selective Inhibitors of AKT1 for Therapeutic Targeting of Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is a major cause of death in developing countries because of high tobacco consumption. RAC-alpha serine-threonine kinase (AKT1) is considered as an attractive drug target because its prolonged activation and overexpression are associated with cancer progression and metastasis. In addition, several AKT1 inhibitors are being developed to control OSCC and other associated forms of cancers.

Death-Associated Protein Kinase 3 Inhibitors Identified by Virtual Screening for Drug Discovery in Cancer and Hypertension.

Death-associated protein kinase 3 (DAPK3) is a serine/threonine protein kinase that regulates apoptosis, autophagy, transcription, and actin cytoskeleton reorganization. DAPK3 induces morphological alterations in apoptosis when overexpressed, and it is considered a potential drug target in antihypertensive and anticancer drug development. In this article, we report new findings from a structure-guided virtual screening for discovery of phytochemicals that could modulate the elevated expression of DAPK3, and with an eye to anticancer drug discovery.

Differential Gene Expression and Weighted Correlation Network Dynamics in High-Throughput Datasets of Prostate Cancer.

Precision oncology is an absolute need today due to the emergence of treatment resistance and heterogeneity among cancerous profiles. Target-propelled cancer therapy is one of the treasures of precision oncology which has come together with substantial medical accomplishment. Prostate cancer is one of the most common cancers in males, with tremendous biological heterogeneity in molecular and clinical behavior.

Investigation of sphingosine kinase 1 inhibitory potential of cinchonine and colcemid targeting anticancer therapy.

Sphingosine kinase 1 (SphK1) and sphingosine-1-phosphate (S1P) signaling regulates numerous diseases such as cancer, diabetes, and inflammation-related ailments, rheumatoid arthritis, atherosclerosis, and multiple sclerosis. The importance of SphK1 in chemo-resistance has been extensively explored in breast, lung, colon, and hepatocellular carcinomas. SphK1 is considered an attractive drug target for the development of anticancer therapy.

Identification of natural compounds as potent inhibitors of SARS-CoV-2 main protease using combined docking and molecular dynamics simulations.

Coronavirus disease 2019 (COVID-19) has emerged from China and globally affected the entire population through the human-to-human transmission of a newly emerged virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The genome of SARS-CoV-2 encodes several proteins that are essential for multiplication and pathogenesis. The main protease (M or 3CL) of SARS-CoV-2 plays a central role in its pathogenesis and thus is considered as an attractive drug target for the drug design and development of small-molecule inhibitors.

Structure-based identification of potential SARS-CoV-2 main protease inhibitors.

To address coronavirus disease (COVID-19), currently, no effective drug or vaccine is available. In this regard, molecular modeling approaches are highly useful to discover potential inhibitors of the main protease (M) enzyme of SARS-CoV-2. Since, the M enzyme plays key roles in mediating viral replication and transcription; therefore, it is considered as an attractive drug target to control SARS-CoV-2 infection.

Identification of Sphingosine Kinase-1 Inhibitors from Bioactive Natural Products Targeting Cancer Therapy.

Sphingosine kinase 1 (SphK1) is an oncogenic lipid kinase that catalyzes the formation of sphingosine-1-phosphate via phosphorylation of sphingosine and known to play a crucial role in angiogenesis, lymphocyte trafficking, signal transduction pathways, and response to apoptotic stimuli. SphK1 has received attention because of its involvement in varying types of cancer and inflammatory diseases such as rheumatoid arthritis, diabetes, renal fibrosis, pulmonary fibrosis, asthma, and neurodegenerative disorders. In the malignancies of breast, lung, uterus, ovary, kidney, and leukemia, overexpression of SphK1 has been reported and thus considered as a potential drug target.

Impact of glioblastoma multiforme associated mutations on the structure and function of MAP/microtubule affinity regulating kinase 4.

MAP/Microtubule affinity regulating kinase 4 (MARK4) plays an important role in the regulation of microtubule dynamics by phosphorylation of tau protein. A higher expression of MARK4 is observed in the glioblastoma multiforme (GBM) cell lines. We identified eight synonymous and non-synonymous mutations in the gene related to GBM in The Cancer Genome Atlas (TCGA) consortium.

Investigation of conformational dynamics of Tyr89Cys mutation in protection of telomeres 1 gene associated with familial melanoma.

Protection of telomeres 1 (POT1) is a component of the shelterin complex which is crucial for the regulation of telomere length and maintenance. Many naturally occurring mutations in the POT1 gene have been found to be associated with cardiac angiosarcoma, glioma, familial melanoma, and chronic lymphocytic leukemia. In particular, Y89C is a naturally occurring mutation of POT1, responsible for familial melanoma, and the molecular basis of this mutation is unexplored.

Evaluation of pyrazolopyrimidine derivatives as microtubule affinity regulating kinase 4 inhibitors: Towards therapeutic management of Alzheimer's disease.

Microtubule affinity regulating kinase 4 (MARK4) plays essential role in the tau-assisted regulation of microtubule dynamics. Over expression of MARK4 causes early phosphorylation of Ser262 of tau protein which is essential for microtubule binding. Hyperphosphorylation of tau protein causes the formation of paired helical fragments and neurofibrillary tangles, the hallmarks of Alzheimer's disease.

Identification and evaluation of glutathione conjugate gamma-l-glutamyl-l-cysteine for improved drug delivery to the brain.

Glutathione (GU), an endogenous antioxidant tripeptide, is frequently transferred in the human brain through -methyl-d-aspartate receptor (NMDAR), profusely expressed at the blood-brain barrier (BBB) junction. GU, also modifies the characteristics of tight junction proteins (occludin and claudin) at the site of BBB by depolarizing the enzyme, protein tyrosine phosphatase that manifests its usefulness for passive delivery of nanocarriers to the brain. GU, thus, represents itself as an ideal ligand for the surface decoration of nanocarriers to successfully administer them across the brain via receptor-mediated drug delivery pathway.