Tag: 370.5745

Ethidium bromide exposure unmasks an antibiotic efflux system in Rhodococcus equi was written by Rampacci, Elisa;Marenzoni, Maria Luisa;Cannalire, Rolando;Pietrella, Donatella;Sabatini, Stefano;Giovagnoli, Stefano;Felicetti, Tommaso;Pepe, Marco;Passamonti, Fabrizio. And the article was included in Journal of Antimicrobial Chemotherapy in 2021.Application In Synthesis of 10-(2-(1-Methylpiperidin-2-yl)ethyl)-2-(methylthio)-10H-phenothiazine This article mentions the following:

This study introduces a newly created strain (Rhodococcus equiEtBr25) by exposing R. equi ATCC 33701 to ethidium bromide (EtBr), a substrate for MDR transporters. Such an approach allowed us to investigate the resulting phenotype and genetic mechanisms underlying the efflux-mediated resistance in R. equi. R. equi ATCC 33701 was stimulated with increasing concentrations of EtBr. The antimicrobial susceptibility of the parental strain and R. equiEtBr25 was investigated in the presence/absence of efflux pump inhibitors (EPIs). EtBr efflux was evaluated by EtBr-agar method and flow cytometry. The presence of efflux pump genes was determined by conventional PCR before to quantify the expression of 30 genes coding for membrane transporters by qPCR. The presence of erm(46) and mutations in 23S rRNA, and gyrA/gyrB was assessed by PCR and DNA sequencing to exclude the occurrence of resistance mechanisms other than efflux. R. equiEtBr25 showed an increased EtBr efflux. Against this strain, the activity of EtBr, azithromycin and ciprofloxacin was more affected than that of rifampicin and azithromycin/rifampicin combinations. Resistances were reversed by combining the antimicrobials with EPIs. Gene expression anal. detected a marked up-regulation of REQ_RS13460 encoding for a Major Facilitator Superfamily (MFS) transporter. G→A transition occurred in the transcriptional repressor tetR/acrR adjacent to REQ_RS13460. Exposure of R. equi to EtBr unmasked an efflux-mediated defense against azithromycin and ciprofloxacin, which seemingly correlates with the overexpression of a specific MFS transporter. This genotype may mirror an insidious low-level resistance of clin. important isolates that could be countered by EPI-based therapies. In the experiment, the researchers used many compounds, for example, 10-(2-(1-Methylpiperidin-2-yl)ethyl)-2-(methylthio)-10H-phenothiazine (cas: 50-52-2Application In Synthesis of 10-(2-(1-Methylpiperidin-2-yl)ethyl)-2-(methylthio)-10H-phenothiazine).

10-(2-(1-Methylpiperidin-2-yl)ethyl)-2-(methylthio)-10H-phenothiazine (cas: 50-52-2) belongs to piperidine derivatives. Piperidine is a metabolite of cadaverine, a polyamine found in the human intestine. Fluorinated piperidines are also the subject of continued interest in medicinal chemistry, for example in the synthesis of selective dipeptidyl peptidase II (DPP II) inhibitors. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions.Application In Synthesis of 10-(2-(1-Methylpiperidin-2-yl)ethyl)-2-(methylthio)-10H-phenothiazine

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Classifying Drugs by their Arrhythmogenic Risk Using Machine Learning was written by Sahli-Costabal, Francisco;Seo, Kinya;Ashley, Euan;Kuhl, Ellen. And the article was included in Biophysical Journal in 2020.Recommanded Product: 50-52-2 This article mentions the following:

All medications have adverse effects. Among the most serious of these are cardiac arrhythmias. Current paradigms for drug safety evaluation are costly, lengthy, conservative, and impede efficient drug development. Here, we combine multiscale experiment and simulation, high-performance computing, and machine learning to create a risk estimator to stratify new and existing drugs according to their proarrhythmic potential. We capitalize on recent developments in machine learning and integrate information across 10 orders of magnitude in space and time to provide a holistic picture of the effects of drugs, either individually or in combination with other drugs. We show, both exptl. and computationally, that drug-induced arrhythmias are dominated by the interplay between two currents with opposing effects: the rapid delayed rectifier potassium current and the L-type calcium current. Using Gaussian process classification, we create a classifier that stratifies drugs into safe and arrhythmic domains for any combinations of these two currents. We demonstrate that our classifier correctly identifies the risk categories of 22 common drugs exclusively on the basis of their concentrations at 50% current block. Our new risk assessment tool explains under which conditions blocking the L-type calcium current can delay or even entirely suppress arrhythmogenic events. Using machine learning in drug safety evaluation can provide a more accurate and comprehensive mechanistic assessment of the proarrhythmic potential of new drugs. Our study paves the way toward establishing science-based criteria to accelerate drug development, design safer drugs, and reduce heart rhythm disorders. In the experiment, the researchers used many compounds, for example, 10-(2-(1-Methylpiperidin-2-yl)ethyl)-2-(methylthio)-10H-phenothiazine (cas: 50-52-2Recommanded Product: 50-52-2).

10-(2-(1-Methylpiperidin-2-yl)ethyl)-2-(methylthio)-10H-phenothiazine (cas: 50-52-2) belongs to piperidine derivatives. The piperidine moiety constitutes an important building block for the synthesis of a variety of bioactive natural products, alkaloids and other drugs. Fluorinated piperidines are also the subject of continued interest in medicinal chemistry, for example in the synthesis of selective dipeptidyl peptidase II (DPP II) inhibitors. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions.Recommanded Product: 50-52-2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Allosteric Activators of Protein Phosphatase 2A Display Broad Antitumor Activity Mediated by Dephosphorylation of MYBL2 was written by Morita, Ken;He, Shuning;Nowak, Radoslaw P.;Wang, Jinhua;Zimmerman, Mark W.;Fu, Cong;Durbin, Adam D.;Martel, Megan W.;Prutsch, Nicole;Gray, Nathanael S.;Fischer, Eric S.;Look, A. Thomas. And the article was included in Cell (Cambridge, MA, United States) in 2020.Recommanded Product: 10-(2-(1-Methylpiperidin-2-yl)ethyl)-2-(methylthio)-10H-phenothiazine This article mentions the following:

Protein phosphatase 2A (PP2A) enzymes can suppress tumors, but they are often inactivated in human cancers overexpressing inhibitory proteins. Here, we identify a class of small-mol. iHAPs (improved heterocyclic activators of PP2A) that kill leukemia cells by allosterically assembling a specific heterotrimeric PP2A holoenzyme consisting of PPP2R1A (scaffold), PPP2R5E (B56ε, regulatory), and PPP2CA (catalytic) subunits. One compound, iHAP1, activates this complex but does not inhibit dopamine receptor D2, a mediator of neurol. toxicity induced by perphenazine and related neuroleptics. The PP2A complex activated by iHAP1 dephosphorylates the MYBL2 transcription factor on Ser241, causing irreversible arrest of leukemia and other cancer cells in prometaphase. In contrast, SMAPs, a sep. class of compounds, activate PP2A holoenzymes containing a different regulatory subunit, do not dephosphorylate MYBL2, and arrest tumor cells in G1 phase. Our findings demonstrate that small mols. can serve as allosteric switches to activate distinct PP2A complexes with unique substrates. In the experiment, the researchers used many compounds, for example, 10-(2-(1-Methylpiperidin-2-yl)ethyl)-2-(methylthio)-10H-phenothiazine (cas: 50-52-2Recommanded Product: 10-(2-(1-Methylpiperidin-2-yl)ethyl)-2-(methylthio)-10H-phenothiazine).

10-(2-(1-Methylpiperidin-2-yl)ethyl)-2-(methylthio)-10H-phenothiazine (cas: 50-52-2) belongs to piperidine derivatives. Piperidine has a role as a reagent, a protic solvent, a base, a catalyst, a plant metabolite, a human metabolite and a non-polar solvent. Several piperidine alkaloids isolated from natural herbs, were found to exhibit antiproliferation and antimetastatic effects on various types of cancers both in vitro and in vivo for example Piperine, Evodiamine, Matrine, Berberine and Tetrandine.Recommanded Product: 10-(2-(1-Methylpiperidin-2-yl)ethyl)-2-(methylthio)-10H-phenothiazine

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem