Phytochemicals Withanolide N and Dryobalanolide as Potential Bioactive Leads for Developing Anticancer Drugs Targeting Tyrosine-Protein Kinase Mer.

There is a growing interest in harnessing natural compounds and bioactive phytochemicals to accelerate drug discovery and development, including in the treatment of human cancers. Receptor tyrosine kinases (RTKs) are critical regulators of many fundamental cellular processes and have been implicated in cancer pathogenesis as well as targets for anticancer drug development. The members of TAM, Tyro3, Axl, and MERTK subfamily RTKs, especially Mer, affect immune homeostasis in the tumor microenvironment.

Remodeling of tumour microenvironment: strategies to overcome therapeutic resistance and innovate immunoengineering in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) stands as the most complex and daunting subtype of breast cancer affecting women globally. Regrettably, treatment options for TNBC remain limited due to its clinical complexity. However, immunotherapy has emerged as a promising avenue, showing success in developing effective therapies for advanced cases and improving patient outcomes.

Hybrid of Deep Feature Extraction and Machine Learning Ensembles for Imbalanced Skin Cancer Datasets.

Skin cancer remains one of the most common and deadly forms of cancer, necessitating accurate and early diagnosis to improve patient outcomes. In order to improve classification performance on unbalanced datasets, this study proposes a distinctive approach for classifying skin cancer that utilises both machine learning (ML) and deep learning (DL) methods. We extract features from three different DL models (DenseNet201, Xception, Mobilenet) and concatenate them to create an extensive feature set.

Distinctive roles of aquaporins and novel therapeutic opportunities against cancer.

Aquaporins (AQPs) are integral membrane proteins responsible for facilitating the transmembrane transport of water and small solutes. Their involvement in diverse physiological functions extends to pathological conditions, including cancer, positioning them as promising targets for anticancer therapy. Tumor cells, particularly those with high metastatic potential, exhibit elevated AQP expression, reinforcing their critical role in tumor biology.

Identification of high-affinity Monoamine oxidase B inhibitors for depression and Parkinson's disease treatment: bioinformatic approach of drug repurposing.

Depression and Parkinson's disease (PD) are devastating psychiatric and neurological disorders that require the development of novel therapeutic interventions. Drug repurposing targeting predefined pharmacological targets is a widely use approach in modern drug discovery. Monoamine oxidase B (MAO-B) is a critical protein implicated in Depression and PD.

compounds: A new avenue for ALR-2 inhibition in diabetes mellitus.

Diabetes mellitus (DM) is a prominent contributor to morbidity and mortality in developed nations, primarily attributable to vascular complications such as atherothrombosis occurring in the coronary arteries. Aldose reductase (ALR2), the main enzyme in the polyol pathway, catalyzes the conversion of glucose to sorbitol, leading to a significant buildup of reactive oxygen species in different tissues. It is therefore a prime candidate for therapeutic targeting, and extensive study is currently underway to discover novel natural compounds that can inhibit it.

Structure-based drug-development study against fibroblast growth factor receptor 2: molecular docking and Molecular dynamics simulation approaches.

Developing new therapeutic strategies to target specific molecular pathways has become a primary focus in modern drug discovery science. Fibroblast growth factor receptor 2 (FGFR2) is a critical signaling protein involved in various cellular processes and implicated in numerous diseases, including cancer. Existing FGFR2 inhibitors face limitations like drug resistance and specificity issues.

Strategic Developments in Polymer-Functionalized Liposomes for Targeted Colon Cancer Therapy: An Updated Review of Clinical Trial Data and Future Horizons.

Liposomes, made up of phospholipid bilayers, are efficient nanocarriers for drug delivery because they can encapsulate both hydrophilic and lipophilic drugs. Conventional cancer treatments sometimes involve considerable toxicities and adverse drug reactions (ADRs), which limits their clinical value. Despite liposomes' promise in addressing these concerns, clinical trials have revealed significant limitations, including stability, targeted distribution, and scaling challenges.

Computational and spectroscopic insight into the binding of citral with human transferrin: Targeting neurodegenerative diseases.

The involvement of neuroinflammation in the pathogenesis of neurodegenerative disorders (NDs) is very significant. Currently, only symptomatic treatments exist, and there are no drugs that modify the progression of Alzheimer's disease (AD) or other NDs. Consequently, there is increasing attention on addressing AD-related neuroinflammation using anti-inflammatory compounds and antioxidants.

Systematic computational strategies for identifying protein targets and lead discovery.

Computational algorithms and tools have retrenched the drug discovery and development timeline. The applicability of computational approaches has gained immense relevance owing to the dramatic surge in the structural information of biomacromolecules and their heteromolecular complexes. Computational methods are now extensively used in identifying new protein targets, druggability assessment, pharmacophore mapping, molecular docking, the virtual screening of lead molecules, bioactivity prediction, molecular dynamics of protein-ligand complexes, affinity prediction, and for designing better ligands.

Structure-based screening of FDA-approved drugs identifies potential histone deacetylase 3 repurposed inhibitor: molecular docking and molecular dynamic simulation approaches.

Histone deacetylase 3 (HDAC3) is a member of the histone deacetylase family that has emerged as a crucial target in the quest for novel therapeutic interventions against various complex diseases, including cancer. The repositioning of FDA-approved drugs presents a promising avenue for the rapid discovery of potential HDAC3 inhibitors. In this study, we performed a structure-based virtual screening of FDA-approved drugs obtained from DrugBank.

Understanding the interactions between repurposed drugs sertindole and temoporfin with receptor for advanced glycation endproducts: Therapeutic implications in cancer and metabolic diseases.

Context: In the pursuit of novel therapeutic possibilities, repurposing existing drugs has gained prominence as an efficient strategy. The findings from our study highlight the potential of repurposed drugs as promising candidates against receptor for advanced glycation endproducts (RAGE) that offer therapeutic implications in cancer, neurodegenerative conditions and metabolic syndromes. Through careful analyses of binding affinities and interaction patterns, we identified a few promising candidates, ultimately focusing on sertindole and temoporfin.

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.

and study targeting the development of a L. () loaded Unani Transdermal patch: Implication of Unani Medicine in the treatment of (Dementia).

( L.) has been extensively used orally and topically in treating various neurological disorders, including dementia. The optimum potential of traditional dosage forms of is limited for various reasons.

Targeting PDE4A for therapeutic potential: exploiting drug repurposing approach through virtual screening and molecular dynamics.

cAMP-specific 3',5'-cyclic phosphodiesterase 4 A (PDE4A) holds a pivotal role in modulating intracellular levels of cyclic adenosine monophosphate (cAMP). Targeting PDE4A with novel therapeutic agents shows promise in addressing neurological disorders (e.g.

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.

Diazepam-based covalent modifiers of GPX4 induce ferroptosis in liver cancer cells.

Developing new chemotherapeutics that are structurally and mechanistically unique is needed due to the rapid rise of the cancer incidence across the globe. Here, we report the identification of irreversible, thiol-reactive diazepam derivatives as GPX4 modifiers and nanomolar inducers of ferroptosis in liver cancer cells.

Identifying repurposed drugs as potential inhibitors of Apolipoprotein E: A bioinformatics approach to target complex diseases associated with lipid metabolism and neurodegeneration.

Apolipoprotein E (ApoE), a pivotal contributor to lipid metabolism and neurodegenerative disorders, emerges as an attractive target for therapeutic intervention. Within this study, we deployed an integrated in-silico strategy, harnessing structure-based virtual screening, to identify potential compounds from DrugBank database. Employing molecular docking, we unveil initial hits by evaluating their binding efficiency with ApoE.

Experimental and Computational Insights into the Molecular Interactions between Human Transferrin and Apigenin: Implications of Natural Compounds in Targeting Neuroinflammation.

Neuroinflammation plays a vital role in Alzheimer's disease (AD) pathogenesis and other neurodegenerative disorders (NDs). Presently, only symptomatic treatments are available and no disease-modifying drugs are available for AD and other NDs. Thus, targeting AD-associated neuroinflammation with anti-inflammatory compounds and antioxidants has recently been given much focus.

Identifying Phosphodiesterase-5 Inhibitors with Drug Repurposing Approach: Implications in Vasodysfunctional Disorders.

Phosphodiesterase type 5 (PDE5) is a multidomain protein that plays a crucial role in regulating cellular cyclic guanosine monophosphate (cGMP), a key signaling molecule involved in various physiological processes. Dysregulation of PDE5 and cGMP signaling is associated with a range of vasodysfunctional disorders, necessitating the development of effective therapeutic interventions. This study adopts comprehensive approach, combining virtual screening and molecular dynamics (MD) simulations, to repurpose FDA-approved drugs as potential PDE5 inhibitors.

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.

Identification of mitogen-activated protein kinase 7 inhibitors from natural products: Combined virtual screening and dynamic simulation studies.

Mitogen-activated protein kinase 7 (MAPK7) is a serine/threonine protein kinase that belongs to the MAPK family and plays a vital role in various cellular processes such as cell proliferation, differentiation, gene transcription, apoptosis, metabolism, and cell survival. The elevated expression of MAPK7 has been associated with the onset and progression of multiple aggressive tumors in humans, underscoring the potential of targeting MAPK7 pathways in therapeutic research. This pursuit holds promise for the advancement of anticancer drug development by developing potential MAPK7 inhibitors.