Identification and Analysis of Anticancer Therapeutic Targets from the Polysaccharide Krestin (PSK) and Polysaccharopeptide (PSP) Using Inverse Docking.

The natural compounds PSK and PSP have antitumor and immunostimulant properties. These pharmacological benefits have been documented in vitro and in vivo, although there is no information in silico which describes the action mechanisms at the molecular level. In this study, the inverse docking method was used to identify the interactions of PSK and PSP with two local databases: BPAT with 66 antitumor proteins, and BPSIC with 138 surfaces and intracellular proteins.

Continuous exposure to doxorubicin induces stem cell-like characteristics and plasticity in MDA-MB-231 breast cancer cells identified with the SORE6 reporter.

Purpose: Cancer stem cells (CSCs) account for recurrence and resistance to breast cancer drugs, rendering them a cause of mortality and therapeutic failure. In this study, we examined the effects of exposure to low concentrations of doxorubicin (Dox) on CSCs and non-CSCs from TNBC.

Methods: The effects of Dox were studied using the SORE6 reporter system.

Consensus Pharmacophore Strategy For Identifying Novel SARS-Cov-2 M Inhibitors from Large Chemical Libraries.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main Protease (M) is an enzyme that cleaves viral polyproteins translated from the viral genome and is critical for viral replication. M is a target for anti-SARS-CoV-2 drug development, and multiple M crystals complexed with competitive inhibitors have been reported. In this study, we aimed to develop an M consensus pharmacophore as a tool to expand the search for inhibitors.

Identification of SARS-CoV-2 Main Protease Inhibitors Using Chemical Similarity Analysis Combined with Machine Learning.

SARS-CoV-2 Main Protease (Mpro) is an enzyme that cleaves viral polyproteins translated from the viral genome, which is critical for viral replication. Mpro is a target for anti-SARS-CoV-2 drug development. Herein, we performed a large-scale virtual screening by comparing multiple structural descriptors of reference molecules with reported anti-coronavirus activity against a library with >17 million compounds.

Changes in neuroinflammatory markers and microglial density in the hippocampus and prefrontal cortex of the C58/J mouse model of autism.

Autism spectrum disorder (ASD) is a diverse group of neurodevelopmental conditions with complex origins. Individuals with ASD present various neurobiological abnormalities, including an altered immune response in the central nervous system and other tissues. Animal models like the C58/J inbred mouse strain are used to study biological characteristics of ASD.

Anthocyanins: Molecular Aspects on Their Neuroprotective Activity.

Anthocyanins are a type of flavonoids that give plants and fruits their vibrant colors. They are known for their potent antioxidant properties and have been linked to various health benefits. Upon consumption, anthocyanins are quickly absorbed and can penetrate the blood-brain barrier (BBB).

Neuroprotective Agents with Therapeutic Potential for COVID-19.

COVID-19 patients can exhibit a wide range of clinical manifestations affecting various organs and systems. Neurological symptoms have been reported in COVID-19 patients, both during the acute phase of the illness and in cases of long-term COVID. Moderate symptoms include ageusia, anosmia, altered mental status, and cognitive impairment, and in more severe cases can manifest as ischemic cerebrovascular disease and encephalitis.

Role of CD36 in cancer progression, stemness, and targeting.

CD36 is highly expressed in diverse tumor types and its expression correlates with advanced stages, poor prognosis, and reduced survival. In cancer cells, CD36: 1) increases fatty acid uptake, reprogramming lipid metabolism; 2) favors cancer cell proliferation, and 3) promotes epithelial-mesenchymal transition. Furthermore, CD36 expression correlates with the expression of cancer stem cell markers and CD36 cancer cells display increased stemness functional properties, including clonogenicity, chemo- and radioresistance, and metastasis-initiating capability, suggesting CD36 is a marker of the cancer stem cell population.

DRD1 and DRD4 are differentially expressed in breast tumors and breast cancer stem cells: pharmacological implications.

Background: Abnormal expression of dopamine receptors (DRs) has been described in multiple tumors, but their roles in breast cancer are inconclusive or contradictory since evidence of pro- and anti-tumoral effects have been reported. Herein, we analyzed the expression of DRs in breast cancer, especially in the subpopulation of cancer stem cells (CSCs), and evaluated the functional role of the receptors by pharmacological targeting.

Methods: Expression of , , , and was investigated in human breast tumors and cancer cell lines using public databases.

Repositioning of Etravirine as a Potential CK1ε Inhibitor by Virtual Screening.

CK1ε is a key regulator of WNT/β-catenin and other pathways that are linked to tumor progression; thus, CK1ε is considered a target for the development of antineoplastic therapies. In this study, we performed a virtual screening to search for potential CK1ε inhibitors. First, we characterized the dynamic noncovalent interactions profiles for a set of reported CK1ε inhibitors to generate a pharmacophore model, which was used to identify new potential inhibitors among FDA-approved drugs.

The interplay between estrogen receptor beta and protein kinase C, a crucial collaboration for medulloblastoma cell proliferation and invasion.

Medulloblastoma (MB) is the most common and aggressive pediatric intracranial tumor. Estrogen receptor β (ERβ) expression correlates with MB development and its phosphorylation modifies its transcriptional activity in a ligand-dependent or independent manner. Using in silico tools, we have identified several residues in ERβ protein as potential targets of protein kinases C (PKCs) α and δ.

Bioassays for the Evaluation of Target Neutralization and Complement-Dependent Cytotoxicity (CDC) of Therapeutic Antibodies.

Therapeutic monoclonal antibodies (mAbs) are complex bioengineered proteins that require to be routinely characterized with robust and reliable bioassays. Infliximab was the first anti-TNFα mAb approved for use in humans and its use has revolutionized the treatment TNF-mediated inflammatory disorders. The mechanism of action (MOA) of infliximab involves its binding to soluble (s) and membrane (m) TNFα.

Synthetic Peptides That Antagonize the Angiotensin-Converting Enzyme-2 (ACE-2) Interaction with SARS-CoV-2 Receptor Binding Spike Protein.

The SARS-CoV-2 viral spike protein S receptor-binding domain (S-RBD) binds ACE2 on host cells to initiate molecular events, resulting in intracellular release of the viral genome. Therefore, antagonists of this interaction could allow a modality for therapeutic intervention. Peptides can inhibit the S-RBD:ACE2 interaction by interacting with the protein-protein interface.

Dopamine Receptors in Cancer: Are They Valid Therapeutic Targets?

The dopamine receptors (DRs) family includes 5 members with differences in signal transduction and ligand affinity. Abnormal DRs expression has been correlated multiple tumors with their clinical outcome. Thus, it has been proposed that DRs-targeting drugs-developed for other diseases as schizophrenia or Parkinson's disease-could be helpful in managing neoplastic diseases.

Progesterone Receptor Together with PKCα Expression as Prognostic Factors for Astrocytomas Malignancy.

Introduction: Astrocytomas are the most common and aggressive primary brain tumors, and they are classified according to the degree of malignancy on a scale of I to IV, in which grade I is the least malignant and grade IV the highest. Many factors are related to astrocytomas progression as progesterone receptor (PR), whose transcriptional activity could be regulated by phosphorylation by protein kinase C alpha (PKCα) at the residue Ser400. Our aim was to investigate if PR phosphorylation together with PKCα expression could be used as a prognostic factor for astrocytomas malignancy.

Repurposing the HCV NS3-4A protease drug boceprevir as COVID-19 therapeutics.

The rapid growth of COVID-19 cases is causing an increasing death toll and also paralyzing the world economy. drug discovery takes years to move from idea and/or pre-clinic to market, and it is not a short-term solution for the current SARS-CoV-2 pandemic. Drug repurposing is perhaps the only short-term solution, while vaccination is a middle-term solution.

In Silico Design and Selection of New Tetrahydroisoquinoline-Based CD44 Antagonist Candidates.

CD44 promotes metastasis, chemoresistance, and stemness in different types of cancer and is a target for the development of new anti-cancer therapies. All CD44 isoforms share a common N-terminal domain that binds to hyaluronic acid (HA). Herein, we used a computational approach to design new potential CD44 antagonists and evaluate their target-binding ability.

Anti-PD-1 And Anti-PD-L1 Antibodies as Immunotherapy Against Cancer: A Structural Perspective.

Programmed cell death protein 1 (PD-1) and its ligand, programmed death-ligand-1 (PD-L1), play key roles in the suppression of the cytotoxic activity of T cells. PD-L1 is overexpressed on various types of cancer cells, leading to immune evasion. In the past decade, therapeutic antibodies that target the PD-1/PD-L1 axis have been developed to inhibit the immune suppression triggered by these two proteins.

Reverse Docking for the Identification of Molecular Targets of Anticancer Compounds.

Molecular docking is a useful and powerful computational method for the identification of potential interactions between small molecules and pharmacological targets. In reverse docking, the ability of one or a few compounds to bind a large dataset of proteins is evaluated in silico. This strategy is useful for identifying molecular targets of orphan bioactive compounds, proposing new molecular mechanisms, finding alternative indications of drugs, or predicting drug toxicity.

Antibody-drug conjugates: the new generation of biotechnological therapies against cancer.

Therapeutic antibodies are recombinant proteins used in the treatment of cancer. There is a new generation of monoclonal antibodies with activity against cancer cells, known as antibody-drug conjugates. These molecules are made up of three elements: a monoclonal antibody, a highly potent cytotoxic drug, and a chemical linker that binds them together.

Pranlukast Antagonizes CD49f and Reduces Stemness in Triple-Negative Breast Cancer Cells.

Introduction: Cancer stem cells (CSCs) drive the initiation, maintenance, and therapy response of breast tumors. CD49f is expressed in breast CSCs and functions in the maintenance of stemness. Thus, blockade of CD49f is a potential therapeutic approach for targeting breast CSCs.

Scaffolding-Induced Property Modulation of Chemical Space.

Physicochemical property switching of chemical space is of great importance for optimization of compounds, for example, for biological activity. Cyclization is a key method to control 3D and other properties. A two-step approach, which involves a multicomponent reaction followed by cyclization, is reported to achieve the transition from basic moieties to charge neutral cyclic derivatives.

CD80 Expression Correlates with IL-6 Production in THP-1-Like Macrophages Costimulated with LPS and Dialyzable Leukocyte Extract (Transferon®).

Transferon® is a complex drug based on a mixture of low molecular weight peptides. This biotherapeutic is employed as a coadjuvant in clinical trials of several diseases, including viral infections and allergies. Given that macrophages play key roles in pathogen recognition, phagocytosis, processing, and antigen presentation, we evaluated the effect of Transferon® on phenotype and function of macrophage-like cells derived from THP-1 monocytes.

Validation of a cell-based colorimetric reporter gene assay for the evaluation of Type I Interferons.

The biotherapeutic type I interferons (IFN-I) are indicated to treat several diseases. These products are regulated to guarantee safety and efficacy through critical quality attributes. For this purpose, the development of robust assays is required, followed by its validation to demonstrate their suitability for its intended purpose.

Transcriptome-based identification of lovastatin as a breast cancer stem cell-targeting drug.

Background: Breast cancer is a neoplastic disease with high morbidity and mortality in women worldwide. Breast cancer stem cells (CSCs) have a significant function in tumor growth, recurrence, and therapeutic resistance. Thus, CSCs have been pointed as targets of new therapies for breast cancer.