Day: November 30, 2022

Zhou, Wei published the artcileInfluence of batch effect correction methods on drug induced differential gene expression profiles, Recommanded Product: 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is batch effect correction method drug differential gene expression; Batch effect; Drug repositioning; Microarray.

Batch effects were not accounted for in most of the studies of computational drug repositioning based on gene expression signatures. It is unknown how batch effect removal methods impact the results of signature-based drug repositioning. Herein, we conducted differential analyses on the Connectivity Map (CMAP) database using several batch effect correction methods to evaluate the influence of batch effect correction methods on computational drug repositioning using microarray data and compare several batch effect correction methods. Differences in average signature size were observed with different methods applied. The gene signatures identified by the Latent Effect Adjustment after Primary Projection (LEAPP) method and the methods fitted with Linear Models for Microarray Data (limma) software demonstrated little agreement. The external validity of the gene signatures was evaluated by connectivity mapping between the CMAP database and the Library of Integrated Network-based Cellular Signatures (LINCS) database. The results of connectivity mapping indicate that the genes identified were not reliable for drugs with total sample size (drug + control samples) smaller than 40, irresp. of the batch effect correction method applied. With total sample size larger than 40, the methods correcting for batch effects produced significantly better results than the method with no batch effect correction. In a simulation study, the power was generally low for simulated data with sample size smaller than 40. We observed best performance when using the limma method correcting for two principal components. Batch effect correction methods strongly impact differential gene expression anal. when the sample size is large enough to contain sufficient information and thus the downstream drug repositioning. We recommend including two or three principal components as covariates in fitting models with limma when sample size is sufficient (larger than 40 drug and controls combined).

BMC Bioinformatics published new progress about Computational biology. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Recommanded Product: 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Lei, Jianzhen published the artcileAberrant Exon 8/8a Splicing by Downregulated PTBP (Polypyrimidine Tract-Binding Protein) 1 Increases CaV1.2 Dihydropyridine Resistance to Attenuate Vasodilation, Product Details of C17H18N2O6, the main research area is PTBP1 exon8 8a splicing CaV12 dihydropyridine resistance vasodilation hypertension; alternative splicing; calcium channel blockers; calcium channels, L-type; hypertension; polypyrimidine tract-binding protein; vasodilation.

Calcium channel blockers, such as dihydropyridines, are commonly used to inhibit enhanced activity of vascular CaV1.2 channels in hypertension. However, patients who are insensitive to such treatments develop calcium channel blocker-resistant hypertension. The function of CaV1.2 channel is diversified by alternative splicing, and the splicing factor PTBP (polypyrimidine tract-binding protein) 1 influences the utilization of mutually exclusive exon 8/8a of the CaV1.2 channel during neuronal development. Nevertheless, whether and how PTBP1 makes a role in the calcium channel blocker sensitivity of vascular CaV1.2 channels, and calcium channel blocker-induced vasodilation remains unknown. We detected high expression of PTBP1 and, inversely, low expression of exon 8a in CaV1.2 channels (CaV1.2E8a) in rat arteries. In contrast, the opposite expression patterns were observed in brain and heart tissues. In comparison to normotensive rats, the expressions of PTBP1 and CaV1.2E8a channels were dysregulated in mesenteric arteries of hypertensive rats. Notably, PTBP1 expression was significantly downregulated, and CaV1.2E8a channels were aberrantly increased in dihydropyridine-resistant arteries compared with dihydropyridine-sensitive arteries of rats and human. In rat vascular smooth muscle cells, PTBP1 knockdown resulted in shifting of CaV1.2 exon 8 to 8a. Using patch-clamp recordings, we demonstrated a concomitant reduction of sensitivity of CaV1.2 channels to nifedipine, due to the higher expression of CaV1.2E8a isoform. In vascular myog. experiments, small interfering RNA-mediated knockdown of PTBP1 attenuated nifedipine-induced vasodilation of rat mesenteric arteries. PTBP1 finely modulates the sensitivities of CaV1.2 channels to dihydropyridine by shifting the utilization of exon 8/8a and resulting in changes of responses in dihydropyridine-induced vasodilation.

Arteriosclerosis, Thrombosis, and Vascular Biology published new progress about Animal gene Role: BSU (Biological Study, Unclassified), PRP (Properties), BIOL (Biological Study) (PTBP1). 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Product Details of C17H18N2O6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Choi, Ji Won published the artcileOptimization of vinyl sulfone derivatives as potent nuclear factor erythroid 2-related factor 2 (Nrf2) activators for Parkinson’s disease therapy, Computed Properties of 71255-09-9, the main research area is vinyl sulfone derivative Nrf2 activator Parkinson disease therapy.

We previously developed a novel series of vinyl sulfones as nuclear factor erythroid 2-related factor 2 (Nrf2) activators with therapeutic potential for Parkinson’s disease (PD). However, the previously developed lead compound (1) exhibited undesirable druglike properties. Here, we optimized vinyl sulfones by introducing nitrogen heterocycles to improve druglike properties. Among the synthesized compounds, 17e was the most promising drug candidate with good druglike properties. Compound 17e showed superior effects on Nrf2 activation in cell-based assays compared to compound 1 (17e: half-maximal effective concentration (EC50) = 346 nM; 1: EC50 = 530 nM). Compound 17e was further confirmed to induce expression of Nrf2-dependent antioxidant enzymes at both mRNA and protein levels. In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of PD, 17e significantly attenuated loss of tyrosine hydroxylase-immunopos. dopaminergic neurons, suppressed microglial activation, and alleviated PD-associated motor dysfunction. Thus, 17e is a novel Nrf2 activator with excellent druglike properties and represents a potential therapeutic candidate for PD.

Journal of Medicinal Chemistry published new progress about Animal gene Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (HO-1, expression induction). 71255-09-9 belongs to class pyridine-derivatives, name is 2-Methoxynicotinaldehyde, and the molecular formula is C7H7NO2, Computed Properties of 71255-09-9.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Gawri, Rahul published the artcileThe anabolic effect of inorganic polyphosphate on chondrocytes is mediated by calcium signalling, Product Details of C17H18N2O6, the main research area is gadolinium SOX9 18S rRNA Coll1A1 Coll X; calcium; calcium signalling; chondrocytes; inorganic polyphosphate.

Inorganic polyphosphates (polyP) are polymers composed of phosphate residues linked by energy-rich phosphoanhydride bonds. As polyP can bind calcium, the hypothesis of this study is that polyP enters chondrocytes and exerts its anabolic effect by calcium influx through calcium channels. PolyP treatment of cartilage tissue formed in 3D culture by bovine chondrocytes showed an increase in proteoglycan accumulation but only when calcium was also present at a concentration of 1.5 mM. This anabolic effect could be prevented by treatment with either ethylene glycol-bis(β-aminoethyl ether)-N,N,N,N-tetraacetic acid or the calcium channel inhibitors gadolinium and nifedipine. Calcium and polyP cotreatment of chondrocytes in monolayer culture resulted in calcium oscillations that were polyP chain length specific and were inhibited by gadolinium and nifedipine. The calcium influx resulted in increased gene expression of sox9, collagen type II, and aggrecan which was prevented by treatment with either calphostin, an inhibitor of protein kinase C, and W7, an inhibitor of calmodulin; suggesting activation of the protein kinase C-calmodulin pathway. Tracing studies using 4,6-diamidino-2-phenylindole, Mitotracker Red, and/or Fura-AM staining showed that polyP was detected in the nucleus, mitochondria, and intracellular vacuoles suggesting that polyP may also enter the cell. PolyP colocalizes with calcium in mitochondria. This study demonstrates that polyP requires the influx of calcium to regulate chondrocyte matrix production, likely via activating calcium signaling. These findings identify the mechanism regulating the anabolic effect of polyP in chondrocytes which will help in its clin. translation into a therapeutic agent for cartilage repair.

Journal of Orthopaedic Research published new progress about Animal gene Role: BSU (Biological Study, Unclassified), PRP (Properties), BIOL (Biological Study) (Coll X). 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Product Details of C17H18N2O6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Hu, Min-Qi published the artcileA one-pot approach to construct 3-(2-methoxypyridin-3-yl)-4H-chromen-4-ones via meinwald rearrangement/intramolecular demethylation annulation of epoxides, Application In Synthesis of 71255-09-9, the main research area is methoxypyridinyloxiranyl methoxyphenylmethanone tandem one pot Meinwald demethylation heterocyclization; methoxypyridinyl chromenone preparation phenylboronic acid palladium catalyst Suzuki coupling; phenyl methoxypyridinyl chromenone preparation.

A convenient and practical approach for construction of 3-(2-methoxypyridin-3-yl)-4H-chromen-4-ones was successfully developed by a one-pot Meinwald rearrangement/intramol. demethylation/annulation reaction sequence with easily accessible epoxides as the starting material. The synthetic protocol was of excellent functional group compatibility under mild reaction conditions, and 3-(2-methoxypyridin-3-yl)-4H-chromen-4-ones were obtained in high yields. Moreover, further derivation successfully furnished more complicated derivatives by Suzuki-Miyaura cross-coupling reaction which may provide a promising potential application in exploring biol. activity of 3-aryl-4H-chromen-4-ones.

Heterocycles published new progress about Demethylation. 71255-09-9 belongs to class pyridine-derivatives, name is 2-Methoxynicotinaldehyde, and the molecular formula is C7H7NO2, Application In Synthesis of 71255-09-9.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Trawny, Daniel published the artcileModular syntheses of star-shaped pyridine, bipyridine, and terpyridine derivatives by employing Sonogashira reactions, Application of Ethyl 6-chloropicolinate, the main research area is pyridine preparation; trialkyne pyridine Sonogashira reaction; bipyridine preparation; bromo bipyridine trialkyne Sonogashira reaction; terpyridine preparation; nonaflate terpyridine trialkyne Sonogashira reaction.

A simple and flexible synthesis for a series C3-sym. core units of star-shaped pyridine e.g., I, bipyridine e.g., II and terpyridine derivatives e.g., III by employing a Sonogashira reaction in the crucial final step was described. A star-shaped dodecafluorinated compound I was also prepared in a straightforward fashion. A simple procedure for the preparation of partially silylated 1,3,5-triethynylbenzene derivatives was presented, which provides an approach to C2-sym. star-shaped compounds that have only one terpyridine and two terphenyl units as ‘dummy’ ligands. The absorption and emission spectra of the fully conjugated C3-sym. pyridine derivatives were systematically investigated, and fairly large Stokes shifts were observed

European Journal of Organic Chemistry published new progress about Pyridines Role: PRP (Properties), RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 21190-89-6 belongs to class pyridine-derivatives, name is Ethyl 6-chloropicolinate, and the molecular formula is C8H8ClNO2, Application of Ethyl 6-chloropicolinate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Lauro, Figueroa-Valverde published the artcileEvaluation of Biological Activity of a Diazocine Derivative against Heart Failure Using an Ischemia-Reperfusion Injury Model, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is heart failure ischemia reperfusion injury diazocine.

BackgroundThere are studies, which suggest that some diazocine derivatives can exert effects on the cardiovascular system; however, these effects are not very clear. ObjectiveThe aim of this research was to evaluate the biol. activity of a diazocine derivative against heart failure translated as area infarct. MethodsBiol. activity produced by diazocine derivatives against heart failure was determinate using an ischemia/reperfusion injury model. Besides, to characterize the mol. mechanism of effect exerted by diazocine derivative on left ventricular pressure (LVP) was determinate in an isolated rat heart model using nifedipine, PINAME TXA 2, and quinalizarin as controls. ResultsThe results showed that diazocine derivative decrease the infarct area and increase the LVP. However, the effect produced by diazocine derivative on LVP was inhibited in the presence of quinalizarin. ConclusionsThe results indicate that biol. activity produced by diazocine derivative on left ventricular pressure is through protein CK2 activation; this phenomenon could be translated as a decrease in both infarct area and heart failure.

Drug Research (Stuttgart, Germany) published new progress about Biology. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Savarimuthu, Sebastian Antony published the artcileDBU-Mediated Intermolecular 5-exo-dig Cyclization of Propargyl Alcohols and Carbon Disulfide to [1,3]-Oxathiole-2-thiones, Computed Properties of 71255-09-9, the main research area is propargyl alc preparation carbon disulfide DBU regioselective cyclization; aryl oxathiole thione preparation.

A novel metal-free method was proposed to produce [1,3]-oxathiole-2-thiones from a readily synthesized propargyl alcs. and easily accessible carbon disulfide, where both secondary and primary propargyl alcs. were compatible to this methodol. This procedure was simple, versatile, atom economy and functional group tolerance resulting in moderate to excellent yields. Finally, the process was screened on different mode of reaction operation.

ChemistrySelect published new progress about Alkynyl alcohols Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 71255-09-9 belongs to class pyridine-derivatives, name is 2-Methoxynicotinaldehyde, and the molecular formula is C7H7NO2, Computed Properties of 71255-09-9.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Tayama, Eiji published the artcileBase-induced Sommelet-Hauser rearrangement of N-(pyridinylmethyl) tetraalkylammonium salts, HPLC of Formula: 24484-93-3, the main research area is acylmethyl pyridylammonium bromide Sommelete Hauser rearrangement bond activation; acyl aminomethylpyridine preparation.

The base-induced Sommelet-Hauser (S-H) rearrangement of various types of N-(pyridinylmethyl) tetraalkylammonium salts to produce N,N-dialkyl-α-pyridinylamino acid esters were investigated. For example, a treatment of N-(2-pyridinylmethyl) glycine tert-Bu ester-derived tetraalkylammonium salt with 1.2 equiv of potassium tert-butoxide in THF at -40°C gave the corresponding S-H product, I [R = Obut; R1 = R2 = Me; R3= H] in 93% yield. Method was an efficient C-H functionalization of pyridines under simple and mild conditions.

Tetrahedron published new progress about Aralkyl halides Role: RCT (Reactant), RACT (Reactant or Reagent). 24484-93-3 belongs to class pyridine-derivatives, name is Methyl 4-chloropicolinate, and the molecular formula is C7H6ClNO2, HPLC of Formula: 24484-93-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem