A novel BH3 mimetic Bcl-2 inhibitor promotes autophagic cell death and reduces in vivo Glioblastoma tumor growth.

Anti-apoptotic members of the Bcl-2 family proteins play central roles in the regulation of cell death in glioblastoma (GBM), the most malignant type of brain tumor. Despite the advances in GBM treatment, there is still an urgent need for new therapeutic approaches. Here, we report a novel 4-thiazolidinone derivative BH3 mimetic, BAU-243 that binds to Bcl-2 with a high affinity.

The neutralization effect of montelukast on SARS-CoV-2 is shown by multiscale in silico simulations and combined in vitro studies.

Small molecule inhibitors have previously been investigated in different studies as possible therapeutics in the treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In the current drug repurposing study, we identified the leukotriene (D4) receptor antagonist montelukast as a novel agent that simultaneously targets two important drug targets of SARS-CoV-2. We initially demonstrated the dual inhibition profile of montelukast through multiscale molecular modeling studies.

Screening of Clinically Approved and Investigation Drugs as Potential Inhibitors of SARS-CoV-2: A Combined in silico and in vitro Study.

In the current study, we used 7922 FDA approved small molecule drugs as well as compounds in clinical investigation from NIH's NPC database in our drug repurposing study. SARS-CoV-2 main protease as well as Spike protein/ACE2 targets were used in virtual screening and top-100 compounds from each docking simulations were considered initially in short molecular dynamics (MD) simulations and their average binding energies were calculated by MM/GBSA method. Promising hit compounds selected based on average MM/GBSA scores were then used in long MD simulations.

Near-physiological-temperature serial crystallography reveals conformations of SARS-CoV-2 main protease active site for improved drug repurposing.

The COVID-19 pandemic has resulted in 198 million reported infections and more than 4 million deaths as of July 2021 (covid19.who.int).

Association of MTHFR, MTRR and RAD54L Gene Variations with Meningioma and Correlation with Tumor's Histopathological Characteristics on Turkish Cohort.

Aim: To elucidate the association of the MTHFR, MTRR, and RAD54L gene variations with meningioma in Turkish cohort.

Material And Methods: DNAs were isolated from 87 retrospective meningioma samples. The MTHFR, MTRR, and RAD54L gene hotspot regions were amplified with specific primers via polymerase chain reaction (PCR), and next-generation sequencing (NGS) was performed.

Genome-wide identification of Chiari malformation type I associated candidate genes and chromosomal variations.

Chiari malformation type I (CMI) is a brain malformation that is characterized by herniation of the cerebellum into the spinal canal. Chiari malformation type I is highly heterogeneous; therefore, an accurate explanation of the pathogenesis of the disease is often not possible. Although some studies showed the role of genetics in CMI, the involvement of genetic variations in CMI pathogenesis has not been thoroughly elucidated.

Integrating Ligand and Target-Driven Based Virtual Screening Approaches With Human Cell Line Models and Time-Resolved Fluorescence Resonance Energy Transfer Assay to Identify Novel Hit Compounds Against BCL-2.

Antiapoptotic members of -/-2 (BCL-2) family proteins are one of the overexpressed proteins in cancer cells that are oncogenic targets. As such, targeting of BCL-2 family proteins raises hopes for new therapeutic discoveries. Thus, we used multistep screening and filtering approaches that combine structure and ligand-based drug design to identify new, effective BCL-2 inhibitors from a small molecule database (Specs SC), which includes more than 210,000 compounds.