Current Pharmaceutical Design - Volume 26, Issue 44, 2020

The Block Relevance (BR) analysis with its recent implementation in MATLAB is a computational tool that allows deconvoluting the balance of intermolecular interactions governing a given drug discoveryrelated phenomenon described by a QSPR/PLS model. Here we discuss a few applications to show how BR analysis can make faster and more efficient the assessment of the drug-likeness of drug candidates. First, Read More

Background: The growing evidence that G protein-coupled receptors (GPCRs) not only form oligomers but that the oligomers also may modulate the receptor function provides a promising avenue in the area of drug design. Highly selective drugs targeting distinct oligomeric sub-states offer the potential to increase efficacy while reducing side effects. In this regard, determining the various oligomeric configurations and geom Read More

Drug discovery efforts for new covalent inhibitors have drastically increased in the last few years. The binding mechanism of covalent compounds entails the formation of a chemical bond between their electrophilic warhead group and the protein of interest. The use of moderately reactive warheads targeting nonconserved nucleophilic residues can improve the affinity and selectivity profiles of covalent binders as compared Read More

Combinations of different technologies are at the heart of the development and implementation of new, innovative processes and approaches for Industry 4.0 in the field of medicinal chemistry and drug discovery. Process intensification and advances in high-throughput synthetic techniques can dramatically improve reaction rates in processes for which slow kinetics represents a bottleneck. Easier access to target-based che Read More

Background: As not all target proteins can be easily screened in vitro, advanced virtual screening is becoming critical. Objective: In this study, we demonstrate the application of reinforcement learning guided virtual screening for γ-aminobutyric acid A receptor (GABAAR) modulating peptides. Methods: Structure-based virtual screening was performed on a receptor homology model. Screened molecules deemed to be novel we Read More

Background: Skin is the largest organ of the body and helps to regulate several physiological functions. It acts as a barrier that protects the body against UV-radiation, toxic substances, infections, etc. The abnormal growth of the skin cells is called skin cancer. Different types of skin cancer can be classified as Basal Cell Carcinoma (BCC) and Squamous Cell Carcinoma (SCC); which mainly occur due to chronic exposure to UV- su Read More

Background: Meteorin-like (Metrnl) is a newly identified adipokine implicated in the pathogenesis of type 2 diabetes mellitus (T2DM), yet data on the circulating levels of Metrnl in patients with T2DM are controversial. To derive a more precise estimation on circulating Metrnl levels in T2DM patients, we conducted this meta-analysis. Methods: The existing studies on the circulating levels of Metrnl in patients with T2DM publish Read More

Objective: The aim was to evaluate the efficacy and safety of duration of dual antiplatelet therapy (DAPT) for patients who received percutaneous coronary intervention (PCI) with a drug-eluting stent. Background: The optimal duration of DAPT to balance the risk of ischemia and bleeding in CAD patients undergoing drug-eluting stent (DES) implantation remains controversial. Methods: PubMed, Cochrane Library, Web of Science, Read More

Background: Zacopride, a potent antagonist of 5-HT3 receptors and an agonist of 5-HT4 receptors, is a gastrointestinal prokinetic agent. In a previous study, we discovered that zacopride selectively stimulated the inward rectifier potassium current (IK1) in the rat and that agonizing IK1 prevented or eliminated aconitine-induced arrhythmias in rats. Objective: Our aims were to confirm that the antiarrhythmic effects of za Read More

Background: Oxaliplatin (OXP), a 3rd generation platinum compound, which causes severe side effects due to; impulse high concentration in the bloodstream thereby exposing healthy cells at a high ratio, nonspecific delivery at the target site and non-compliance is administered intravenously. Objective: The project was aimed at the development, characterization, and in-vitro and in-vivo evaluation of pHresponsive hydrogels fo Read More