Tag: M.W=350-400

Yuan, Zi-Qing-Yun published the artcileImpact of 14 types of genetic polymorphisms on antihypertensive efficacy of felodipine in healthy Chinese subjects, Product Details of C18H19Cl2NO4, the main research area is felodipine genetic polymorphism antihypertensive efficacy.

This study evaluated different influences of 14 single nucleotide polymorphisms (SNPs) and demog. factors leading to individual differences in the antihypertensive efficacy of felodipine in healthy Chinese subjects. 24 Subjects were sequenced for candidate SNPs. Plasma samples were obtained as clin. trial protocol, and were determined by a HPLC-MS/MS method. Pharmacokinetic parameters were calculated by WinNonlin 6.0. Statistical anal. was mainly performed by SPSS 22.0. A multiple linear regression model provided different weight coefficients of different demog. and genetic factors. The trend of Cmax is almost consistent with AUCss increase, but tmax of individuals is different; the antihypertensive effect of felodipine is individually different. A significant association was observed between systolic blood pressure decrease (δSBP) and SNPs of CACNA1C, CACNA1D, GNB3 resp., while CACNA1C and CACNA1 were associated with diastolic blood pressure decrease (δDBP). CYP3A5 rs766746 and CYP3A4 rs2242480 were linked with Cmax and AUCss, and ABCB1 rs1045642 was associated with T1/2. Significant relationships were shown between AUCss and ΔSBP (p = 0.022) as well as Cmax and ΔSBP (p = 0.015). The efficacy of felodipine is individually different, influenced especially by CACNA1C rs1051375 and ABCB1 rs1045642. δDBP is associated with δSBP in multiple-dosing of felodipine in healthy Chinese subjects.

International Journal of Clinical Pharmacology and Therapeutics published new progress about Antihypertensives. 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, Product Details of C18H19Cl2NO4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Brinkmann, Joscha published the artcileSolubility of Pharmaceutical Ingredients in Natural Edible Oils, COA of Formula: C18H19Cl2NO4, the main research area is solubility pharmaceutical ingredient edible oil; PC-SAFT; lipid-based drug delivery systems; oils; solubility.

Natural edible oils (NEOs) are common excipients for lipid-based formulations. Many of them are complex mixtures comprising hundreds of different triglycerides (TGs). One major challenge in developing lipid-based formulations is the variety in NEO compositions affecting the solubility of active pharmaceutical ingredients. In this work, solubilities of indomethacin (IND), ibuprofen (IBU), and fenofibrate (FFB) in soybean oil and in coconut oil were measured via differential scanning calorimetry, high-performance liquid chromatog., and Raman spectroscopy. Furthermore, this work proposes an approach that mimics NEOs using one key TG and models the API solubilities in these NEOs based on perturbed-chain statistical associating fluid theory (PC-SAFT). Key TGs were determined using the 1,2,3-random hypothesis, and PC-SAFT parameters were estimated via a group-contribution method. Using the proposed approach, the solubility of IBU and FFB was modeled in soybean oil and coconut oil. Furthermore, the solubilities of five more APIs (IND, cinnarizine, naproxen, griseofulvin, and felodipine) were modeled in soybean oil. All modeling results were found in very good agreement with the exptl. data. The influence of different NEO kinds on API solubility was examined by comparing FFB and IBU solubilities in soybean oil and refined coconut oil. PC-SAFT was thus found to allow assessing the batch-to-batch consistency of NEO batches in silico.

Molecular Pharmaceutics published new progress about Differential scanning calorimetry. 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, COA of Formula: C18H19Cl2NO4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Zhang, Shutao published the artcileFelodipine blocks osteoclast differentiation and ameliorates estrogen-dependent bone loss in mice by modulating p38 signaling pathway, Quality Control of 72509-76-3, the main research area is osteoclast differentiation bone loss estrogen p38 signaling felodipine; Felodipine; MAPK; Osteoclast differentiation; Osteoporosis; RNA-Seq.

Postmenopausal osteoporosis is one of the most common types of osteoporosis resulting from estrogen deficiency in elderly women. In addition, hypertension is another common disease in the elderly, and it has become an independent risk factor for osteoporosis and osteoporotic fractures. Here, we report for the first time that felodipine, a first-line antihypertensive agent, significantly prevents postmenopausal osteoporosis in addition to its vasodilation properties. Quant. RT-PCR anal. revealed that treatment with felodipine significantly downregulated the genes associated with osteoclast differentiation. RNA-sequencing and western blotting suggested that felodipine could inhibit bone resorption by suppressing MAPK pathway phosphorylation. Moreover, micro-CT scanning and histol. anal. in an ovariectomy (OVX)-induced bone-loss mouse model indicated that felodipine might be a potent drug for preventing osteoporotic fractures. Therefore, this study proposes an attractive and promising agent with vasodilation properties to treat postmenopausal osteoporosis.

Experimental Cell Research published new progress about Animal gene Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (TRAP). 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, Quality Control of 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Fernandes, Hugo J. R. published the artcileSingle-Cell Transcriptomics of Parkinson’s Disease Human In Vitro Models Reveals Dopamine Neuron-Specific Stress Responses, COA of Formula: C18H19Cl2NO4, the main research area is transcriptomics Parkinsons disease dopamine neuron iPSC; Cholesterol biosynthesis; Dopamine neurons; ER stress; Felodipine; Human iPSC; Oxidative stress; PD GWAS; Parkinson’s disease; SNCA-A53T; Single-cell transcriptomics.

The advent of induced pluripotent stem cell (iPSC)-derived neurons has revolutionized Parkinson’s disease (PD) research, but single-cell transcriptomic anal. suggests unresolved cellular heterogeneity within these models. Here, we perform the largest single-cell transcriptomic study of human iPSC-derived dopaminergic neurons to elucidate gene expression dynamics in response to cytotoxic and genetic stressors. We identify multiple neuronal subtypes with transcriptionally distinct profiles and differential sensitivity to stress, highlighting cellular heterogeneity in dopamine in vitro models. We validate this disease model by showing robust expression of PD GWAS genes and overlap with postmortem adult substantia nigra neurons. Importantly, stress signatures are ameliorated using felodipine, an FDA-approved drug. Using isogenic SNCA-A53T mutants, we find perturbations in glycolysis, cholesterol metabolism, synaptic signaling, and ubiquitin-proteasomal degradation Overall, our study reveals cell type-specific perturbations in human dopamine neurons, which will further our understanding of PD and have implications for cell replacement therapies.

Cell Reports published new progress about Animal gene Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (DAn1). 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, COA of Formula: C18H19Cl2NO4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Henze, Laura J. published the artcileDevelopment and evaluation of a biorelevant medium simulating porcine gastrointestinal fluids, Application of 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is gastrointestinal fluid dissolution intestinal medium; Animal model; Bile salts; Biorelevant media; Dissolution test; FaSSIF; FaSSIFp; Gastrointestinal fluid; Pigs; Pre-clinical model; phospholipids.

During drug product development preclin. animal models are also required to assess drug product performance, and there is a need to develop species specific intestinal media to similarly predict in vivo pharmacokinetic profiles in each preclin. model. Pigs, are increasingly being used in preclin. drug development, however to date there is a lack of quant. information about the composition of porcine gastrointestinal (GI) fluids. GI fluid samples, were collected from landrace pigs, and characterized. Fasted State Simulated Intestinal Fluid of pigs (FaSSIFp) was developed based on the physiol. composition of the GI fluids in terms of pH, buffer capacity, osmolality, surface tension, as well as the bile salt, phospholipid and free fatty acid content. This study demonstrated that FaSSIFp was superior at predicting the solubility of the six model drugs in porcine intestinal fluids (PIF). A markedly high correlation (r2 0.98) was observed between the solubility obtained in PIF and FaSSIFp, whereas poor correlation (r2 0.12) was found for the solubility of the model drugs between human FaSSIF and PIF. This confirms that species specific biorelevant intestinal media are crucial to provide more accurate predictions of pharmacokinetic studies in preclin. models. Addnl., the availability of a species specific intestinal medium offers the potential to improve in vitro-in silico approaches to predict in vivo absorption and to reduce the overall number of animals needed in oral drug product development testing.

European Journal of Pharmaceutics and Biopharmaceutics published new progress about Dissolution. 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, Application of 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Alvebratt, Caroline published the artcileAn in vitro dissolution-digestion-permeation assay for the study of advanced drug delivery systems, Category: pyridine-derivatives, the main research area is felodipine oral drug delivery system lipid digestion colorectal cancer; Advanced drug delivery systems; Caco-2 cells; Digestion; Dissolution; Lipid-based formulations; Permeation.

Advanced drug delivery systems (ADDS) are widely explored to overcome poor aqueous solubility of orally administered drugs. However, the prediction of their in vivo performance is challenging, as in vitro models typically do not capture the interplay between processes occurring in the gut. In additions, different models are used to evaluate the different systems. We therefore present a method that allows monitoring of luminal processing (dissolution, digestion) and its interplay with permeation to better inform on the absorption of felodipine formulated as ADDS. Experiments were performed in a μFLUX-apparatus, consisting of two chambers, representing the intestinal and serosal compartment, separated by Caco-2 monolayers. During dissolution-digestion-permeation experiments, ADDS were added to the donor compartment containing simulated intestinal fluid and immobilized lipase. Dissolution and permeation in both compartments were monitored using in situ UV-probes or, when turbidity interfered the measurements, with HPLC anal. The method showed that all ADDS increased donor and receiver concentrations compared to the condition using crystalline felodipine. A poor correlation between the compartments indicated the need for an serosal compartment to evaluate drug absorption from ADDS. The method enables medium-throughput assessment of: (i) dynamic processes occurring in the small intestine, and (ii) drug concentrations in real-time.

European Journal of Pharmaceutics and Biopharmaceutics published new progress about Colorectal neoplasm. 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, Category: pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Zarybnicky, Tomas published the artcileThe selection and validation of reference genes for mRNA and microRNA expression studies in human liver slices using RT-qPCR, Product Details of C18H19Cl2NO4, the main research area is insulin YWHAZ ACTB B2M CYP3A4 CYP1A2 miR165p biomarker steatosis; RT-qPCR; human liver; mRNA; miRNA; precision-cut liver slices; reference gene.

The selection of a suitable combination of reference genes (RGs) for data normalization is a crucial step for obtaining reliable and reproducible results from transcriptional response anal. using a reverse transcription-quant. polymerase chain reaction. This is especially so if a three-dimensional multicellular model prepared from liver tissues originating from biol. diverse human individuals is used. The mRNA and miRNA RGs stability were studied in thirty-five human liver tissue samples and twelve precision-cut human liver slices (PCLS) treated for 24 h with DMSO (controls) and PCLS treated with β-naphthoflavone (10μM) or rifampicin (10μM) as cytochrome P 450 (CYP) inducers. Validation of RGs was performed by an expression anal. of CYP3A4 and CYP1A2 on rifampicin and β-naphthoflavone induction, resp. Regarding mRNA, the best combination of RGs for the controls was YWHAZ and B2M, while YWHAZ and ACTB were selected for the liver samples and treated PCLS. Stability of all candidate miRNA RGs was comparable or better than that of generally used short non-coding RNA U6. The best combination for the control PCLS was miR-16-5p and miR-152-3p, in contrast to the miR-16-5b and miR-23b-3p selected for the treated PCLS. Our results showed that the candidate RGs were rather stable, especially for miRNA in human PCLS.

Genes published new progress about Biomarkers. 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, Product Details of C18H19Cl2NO4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Holt, Kimberly published the artcilePrediction of tissue-plasma partition coefficients using microsomal partitioning: incorporation into physiologically based pharmacokinetic models and steady-state volume of distribution predictions, Formula: C18H19Cl2NO4, the main research area is plasma partition coefficient protein binding microsomal partitioning PBPK model.

Drug distribution is a necessary component of models to predict human pharmacokinetics. A new membrane-based tissue-plasma partition coefficient (Kp) method (Kp,mem) to predict unbound tissue to plasma partition coefficients (Kpu) was developed using in vitro membrane partitioning [fraction unbound in microsomes (fum)], plasma protein binding, and log P. The resulting Kp values were used in a physiol. based pharmacokinetic (PBPK) model to predict the steady-state volume of distribution (Vss) and concentration-time (C-t) profiles for 19 drugs. These results were compared with Kp predictions using a standard method [the differential phospholipid Kp prediction method (Kp,dPL)], which differentiates between acidic and neutral phospholipids. The Kp,mem method was parameterized using published rat Kpu data and tissue lipid composition The Kpu values were well predicted with R2 = 0.8. With one outlier removed for Kp,mem and two for Kp,dPL, the Vss predictions for R2 were 0.80 and 0.79 for the Kp,mem and Kp,dPL methods, resp. The C-t profiles were also predicted and compared. Overall, the Kp,mem method predicted the Vss and C-t profiles equally or better than the Kp,dPL method. An advantage of using fum to parameterize membrane partitioning is that fum data are used for clearance prediction and are, therefore, generated early in the discovery/development process. Also, the method provides a mechanistically sound basis for membrane partitioning and permeability for further improving PBPK models.

Drug Metabolism & Disposition published new progress about Adipose tissue. 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, Formula: C18H19Cl2NO4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Li, Congwei published the artcileSpectroscopic methodology and molecular docking studies on changes in binding interaction of felodipine with bovine serum albumin induced by cocrystallization with β-resorcylic acid, Safety of 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is felodipine bovine serum albumin beta resorcylic acid mol docking; binding interaction; bovine serum albumin; cocrystal; felodipine; molecular docking; β-resorcylic acid.

In the present study, a novel cocrystal of felodipine (FEL) and β-resorcylic acid (βRA) was developed. We specially focused on the change of binding pattern with bovine serum albumin (BSA) induced by cocrystn. of FEL with βRA. The solid characterizations and d. functional theory (DFT) simulation verified that FEL-βRA cocrystal formed in equimolar ratio (1 : 1 M ratio) through C=O···H-O hydrogen bond between C=O group in FEL and O-H group in βRA. The binding interactions between FEL-βRA system and BSA were studied using fluorescence spectral and mol. docking methods. Two guest mol. systems, including a phys. mixture of FEL and βRA and FEL-βRA cocrystal were performed binding to BSA in mol. docking. Mol. docking simulation suggested that FEL and its cocrystal inserted into the subdomain IIIA (site II’) of BSA. The interactions between FEL and BSA including hydrogen bonding with ASN390 residue and intermol. hydrophobic interactions with LEU429 and LEU452 residues. However, the size of supramol. FEL-βRA better matched that of active cavity of BSA; the cocrystal is closely bound to BSA through hydrogen bonding with ASN390 residue and intermol. hydrophobic interactions with LEU429, VAL432, LEU452 and ILE387 residues. This change on binding affinity of FEL to BSA induced by cocrystn. with βRA provided theor. basis to evaluate the transportation, distribution and metabolism of cocrystal drug.

Chemical & Pharmaceutical Bulletin published new progress about Density functional theory. 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, Safety of 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

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