Effect of Fluid Paraffin on the Formulation Properties of Pressure Sensitive Adhesive Formulations Containing Diclofenac Sodium.

Understanding the relationship between the release characteristics of the active ingredient in the tape formulation and the pharmaceutical characteristics of the adhesive layer can optimize therapeutic efficacy and improve patient adherence. This study aimed to clarify the effect of liquid paraffine (LP)/styrene-isoprene-styrene (SIS) triblock copolymer ratio on pressure-sensitive adhesive (PSA) formulation properties, such as adhesive properties and drug release, with a certain amount of diclofenac sodium (DFS) and tackifier. The effects of changes in PSA composition in DFS-containing tape formulations on adhesive and drug release properties were evaluated.

Discovery of Antibacterial Compounds with Potential Multi-Pharmacology against Staphylococcus Family Members by In Silico Structure-Based Drug Screening.

() is a major bacterial infection in humans, leading to severe disease and causing death. The stagnation of antibiotic development in recent decades has made it difficult to combat drug-resistant infections. In this study, we performed an in silico structure-based drug screening (SBDS) targeting the MurE (saMurE) enzyme involved in cell wall synthesis of S.

Data on molecular docking and molecular dynamics targeting shikimic acid kinase.

We have previously performed a hierarchical screening of a shikimic acid kinase [1]. Specifically, 11 compounds were screened from a library of 154,118 compounds provided by ChemBridge [2] using UCSF DOCK [3] and the GOLD [4] program in the first and second steps, respectively. Molecular dynamic simulations were further performed on compound 2 (2-[(5Z)-5-(1-benzyl-5bromo-2-oxoindol-3-(5Z)-5-(1-benzyl-5-bromo-2-oxoindol-3-(5Z)-4-oxo-2 ylidene)-4oxo-2-sulfanylidene-1,3-thiazolidin-3-yl] acetic acid), which showed antimicrobial efficacy.

Identification of Novel Antimicrobial Compounds Targeting -Adenosyl-L-Homocysteine Hydrolase Using Dual Hierarchical In Silico Structure-Based Drug Screening.

The emergence of multidrug-resistant and extensively drug-resistant () has become a major medical problem. -adenosyl-L-homocysteine hydrolase (MtSAHH) was selected as the target protein for the identification of novel anti-TB drugs. Dual hierarchical in silico Structure-Based Drug Screening was performed using a 3D compound structure library (with over 150 thousand synthetic chemicals) to identify compounds that bind to MtSAHH's active site.

Evaluation of a new portable corneal topography system for self-measurement using smartphones: a pilot study.

Purpose: Herein, we propose the use of the "KeraVio Ring", which is a portable, selfie-based, smartphone-attached corneal topography system that is based on the Placido ring videokeratoscope. The goal of this study was to evaluate and compare corneal parameters between KeraVio Ring and conventional corneal tomography images.

Methods: We designed the KeraVio Ring as a device comprising 3D-printed LED rings for generating Placido rings that can be attached to a smartphone.

Computational Screening and Experimental Validation of Inhibitor Targeting the Complex Formation of Grb14 and Insulin Receptor.

The development of drugs targeting gene products associated with insulin resistance holds the potential to enhance our understanding of type 2 diabetes mellitus (T2DM). The virtual screening, based on a three-dimensional (3D) protein structure, is a potential technique to accelerate the development of molecular target drugs. Among the targets implicated in insulin resistance, the genetic characterization and protein function of Grb14 have been clarified without contradiction.

Identification of α-Tocopherol succinate as an RFFL-substrate interaction inhibitor inducing peripheral CFTR stabilization and apoptosis.

The E3 ubiquitin ligase RFFL is an apoptotic inhibitor highly expressed in cancers and its knockdown suppresses cancer cell growth and sensitizes to chemotherapy. RFFL also participates in peripheral protein quality control which removes the functional cell surface ΔF508-CFTR channel and reduces the efficacy of pharmaceutical therapy for cystic fibrosis (CF). Although RFFL inhibitors have therapeutic potential for both cancer and CF, they remain undiscovered.

Identification of novel antimicrobial compounds targeting Mycobacterium tuberculosis shikimate kinase using in silico hierarchical structure-based drug screening.

The development of new anti-TB drugs to prevent the spread of multidrug-resistant Mycobacterium tuberculosis (Mtb) strains is imperative. Mtb shikimate kinase (MtSK) was selected as the target protein to screen for new anti-TB drugs. We performed hierarchical in silico screening using a library of 154,118 compounds to search for novel compounds that could bind to the active site of MtSK.

Identification of Potential Inhibitors against Tyrosyl-tRNA Synthetase.

Background: Drug-resistant () has spread from nosocomial to community-acquired infections. Novel antimicrobial drugs that are effective against resistant strains should be developed. tyrosyl-tRNA synthetase (saTyrRS) is considered essential for bacterial survival and is an attractive target for drug screening.

Identification of a Chemical Inhibitor with a Novel Scaffold Targeting Decaprenylphosphoryl-β-D-Ribose Oxidase (DprE1).

Background: Tuberculosis is the second leading cause of death from infectious diseases worldwide. Multidrug-resistant Mycobacterium tuberculosis is spreading throughout the world, creating a crisis. Hence, there is a need to develop anti-tuberculosis drugs with novel structures and versatile mechanisms of action.

An Inorganic-Organic Hybrid Framework Composed of Polyoxotungstate and Long-Chained Bolaamphiphile.

Surfactants are functional molecules utilized in various situations. The self-assembling property of surfactants enables several molecular arrangements that can be employed to build up nanometer-sized architectures. This is beneficial in the construction of functional inorganic-organic hybrids holding the merits of both inorganic and organic components.

Identification of novel inhibitors for mycobacterial polyketide synthase 13 via in silico drug screening assisted by the parallel compound screening with genetic algorithm-based programs.

Identifying small compounds capable of inhibiting Mycobacterium tuberculosis polyketide synthase 13 (Pks13), in charge of final step of mycolic acid biosynthesis, could lead to the development of a novel antituberculosis drug. This study screened for lead compounds capable of targeting M. tuberculosis Pks13 from a chemical library comprising 154,118 compounds through multiple in silico docking simulations.

Computer-assisted screening of mycobacterial growth inhibitors: Exclusion of frequent hitters with the assistance of the multiple target screening method.

Background: The emergence of frequent hitters (FHs) remains a challenge in drug discovery. We have previously used in silico structure-based drug screening (SBDS) to identify antimycobacterial candidates. However, excluding FHs has not been integrated into the SBDS system.

Structural modification of a novel inhibitor for mycobacterium enoyl-acyl carrier protein reductase assisted by structure-based drug screening.

Background: Mycobacterium tuberculosis enoyl-acyl carrier protein reductase (mtInhA) is involved in the biosynthesis of mycolic acids, a major component of mycobacterial cell walls, and has been targeted in the development of anti-tuberculosis (TB) drugs. In our previous in silico structure-based drug screening study, we identified KES4, a novel class of mtInhA inhibitor. KES4 is composed of four ring structures (A-D-rings) and molecular dynamic simulation predicted that the D-ring is essential for the interaction with mtInhA.

Improvement of the novel inhibitor for Mycobacterium enoyl-acyl carrier protein reductase (InhA): a structure-activity relationship study of KES4 assisted by in silico structure-based drug screening.

InhA or enoyl-acyl carrier protein reductase of Mycobacterium tuberculosis (mtInhA), which controls mycobacterial cell wall construction, has been targeted in the development of antituberculosis drugs. Previously, our in silico structure-based drug screening study identified a novel class of compounds (designated KES4), which is capable of inhibiting the enzymatic activity of mtInhA, as well as mycobacterial growth. The compounds are composed of four ring structures (A-D), and the MD simulation predicted specific interactions with mtInhA of the D-ring and methylene group between the B-ring and C-ring; however, there is still room for improvement in the A-ring structure.

Identification of a novel class of small compounds with anti-tuberculosis activity by in silico structure-based drug screening.

The enzymes responsible for biotin biosynthesis in mycobacteria have been considered as potential drug targets owing to the important role in infection and cell survival that the biotin synthetic pathway plays in Mycobacterium tuberculosis. Among the enzymes that comprise mycobacterium biotin biosynthesis systems, 7,8-diaminopelargonic acid synthase (DAPAS) plays an essential role during the stationary phase in bacterial growth. In this study, compounds that inhibit mycobacterial DAPAS were screened in the virtual chemical library using an in silico structure-based drug screening (SBDS) technique, and the antimycobacterial activity of the selected compounds was validated experimentally.

2,3-Butandione 2-monoxime inhibits skeletal myosin II by accelerating ATP cleavage.

2,3-Butandione 2-monoxime (BDM) is a widely used myosin inhibitor with an unclear mode of action. In this report, we investigated the mechanism of BDM oxime group nucleophilic reactivity on the phosphoester bond of ATP. BDM increased the ATPase activity of skeletal myosin subfragment 1 (S1) under conditions in which ATP cleavage is the rate-limiting step (K, EDTA-ATPase activity of native S1 and Mg-ATPase activity of trinitrophenylated S1 and partially unfolded S1).

structure-based drug screening of novel antimycobacterial pharmacophores by DOCK-GOLD tandem screening.

Background: Enzymes responsible for cell wall development in Mycobacterium tuberculosis are considered as potential targets of anti-tuberculosis (TB) agents. Mycobacterial cyclopropane mycolic acid synthase 1 (CmaA1) is essential for mycobacterial survival because of its critical role in synthesizing mycolic acids.

Materials And Methods: We screened compounds that were capable of interacting with the mycobacterial CmaA1 active site using a virtual compound library with an in silico structure-based drug screening (SBDS).

Tetrahydro-2-furanyl-2,4(1H,3H)-pyrimidinedione derivatives as novel antibacterial compounds against .

Objective/background: Mycobacterium tuberculosis thymidine monophosphate kinase (mtTMPK) is a potential enzymatic target for the treatment of tuberculosis (TB).

Materials And Methods: In this study, we performed pharmacophore-based in silico screening, targeting mtTMPK with a compound library of 461,383 chemicals. We evaluated the candidate compounds for inhibitory effects on the growth of the model mycobacteria, Mycobacterium smegmatis.

Time dilation in a perceptually jittering dot pattern.

Although it is known that a moving stimulus appears to dilate in duration compared to a stationary stimulus, whether subjective motion devoid of stimulus motion is sufficient remains unknown. To elucidate this, we used a motion illusion in which an actually static stimulus clearly appears to move, a useful dissociation between actual and subjective motions. We used the jitter aftereffect resulting from adaptation to dynamic noise as such a tool and measured subjective durations of a static random-dot pattern in which illusory jitter was seen, an actually oscillating pattern mimicking the illusory jitter, and a static pattern without illusory jitter.

Improved production of poly(lactic acid)-like polyester based on metabolite analysis to address the rate-limiting step.

The biosynthesis of poly(lactic acid) (PLA)-like polymers, composed of >99 mol% lactate and a trace amount of 3-hydroxybutyrate, in engineered Corynebacterium glutamicum consists of two steps; the generation of the monomer substrate lactyl-coenzyme A (CoA) and the polyhydroxyalkanoate (PHA) synthase-catalyzed polymerization of lactyl-CoA. In order to increase polymer productivity, we explored the rate-limiting step in PLA-like polymer synthesis based on quantitative metabolite analysis using liquid chromatography mass spectroscopy (LC-MS). A significant pool of lactyl-CoA was found during polymer synthesis.

Discovery of InhA inhibitors with anti-mycobacterial activity through a matched molecular pair approach.

The Mycobacterium tuberculosis (M. tuberculosis) enoyl-acyl carrier protein reductase (mtInhA) is an attractive enzyme and a thoroughly studied target for tuberculosis therapy. In this study, to identify novel structure-activity relationships (SARs) of mtInhA inhibitors, a series of diphenyl ether derivatives were designed based on the matched molecular pair (MMP) method, and the binding energies of these compounds were subsequently estimated by in silico structure-based drug screening (SBDS) to provide more useful data.

Hepatocyte growth factor and Met in drug discovery.

Activation of the hepatocyte growth factor (HGF)-Met pathway evokes dynamic biological responses that support the morphogenesis, regeneration and survival of cells and tissues. A characterization of conditional Met knockout mice indicates that the HGF-Met pathway plays important roles in the regeneration, protection and homeostasis of cells such as hepatocytes, renal tubular cells and neurons. Preclinical studies in disease models have indicated that recombinant HGF protein and expression plasmid for HGF are biological drug candidates for the treatment of patients with diseases or injuries that involve impaired tissue function.

Development of a multiple detection technique for fungi by DNA microarray with the simultaneous use of internal transcribed spacer region of ribosomal RNA gene and β-tubulin gene probes.

We offer the first description of the development of a multiple detection technique for fungi by DNA microarray with the simultaneous use of internal transcribed spacer region (ITS) of ribosomal RNA gene and β-tubulin gene probes. The assay uses 12 oligonucleotide probes and multiplex amplification to detect fungal species belonging to various sections of Aspergillus, the Eurotium genus, and the Penicillium genus. The specificity of each probe was tested using 231 reference fungal strains, including 79 target and 152 non-target strains in 102 species of 24 genera.

Identification of novel potential antibiotics against Staphylococcus using structure-based drug screening targeting dihydrofolate reductase.

The emergence of multidrug-resistant Staphylococcus aureus (S. aureus) makes the treatment of infectious diseases in hospitals more difficult and increases the mortality of the patients. In this study, we attempted to identify novel potent antibiotic candidate compounds against S.