Category: 21829-25-4

Zhang, Yi-Lin published the artcileCellular mechanism underlying the facilitation of contractile response induced by tumor necrosis factor-α in mouse tracheal smooth muscle, Product Details of C17H18N2O6, the publication is American Journal of Pathology (2022), 192(1), 104-111, database is CAplus and MEDLINE.

The proinflammatory cytokine tumor necrosis factor-α (TNF-α) augments intracellular Ca2+ signaling and contractile responses of airway smooth muscles, leading to airway hyperresponsiveness. However, the underlying mechanism has not been fully elucidated. This study aimed to investigate the cellular mechanism of the potentiated contraction of mouse tracheal smooth muscle induced by TNF-α. The results showed that TNF-α triggered facilitation of mouse tracheal smooth muscle contraction in an epithelium-independent manner. The TNF-α-induced hypercontractility could be suppressed by the protein kinase C inhibitor GF109203X, the tyrosine kinase inhibitor genistein, the Src inhibitor PP2, or the L-type voltage-dependent Ca2+ channel blocker nifedipine. Following TNF-α incubation, the α1C L-type Ca2+ channel (CaV1.2) was up-regulated in cultured primary mouse tracheal smooth muscle cells. Pronounced phosphotyrosine levels were observed in mouse tracheas. In conclusion, this study shows that TNF-α enhanced airway smooth muscle contraction via protein kinase C-Src-CaV1.2 pathways, which provides novel insights into the pathol. role of proinflammatory cytokines in mediating airway hyperresponsiveness.

American Journal of Pathology published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C14H10O4S2, Product Details of C17H18N2O6.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Kaburaki, Soyoko published the artcileHepatic drug metabolism in older people with body composition changes., Related Products of pyridine-derivatives, the publication is Geriatrics & gerontology international (2022), 22(5), 449-454, database is MEDLINE.

AIM: Dosage adjustment is essential in older individuals because they are prone to experience a decline in liver function and changes in body composition. However, quantitative tests or equations for evaluating the activity of hepatic drug metabolism have not yet been clearly established. We examined hepatic drug metabolism activities in older individuals, focusing on changes in body composition parameters. METHODS: Lansoprazole and nifedipine, substrates of the metabolic enzymes cytochrome P450 (CYP) 2C19 and 3A4, respectively, were selected to study hepatic drug metabolism. Residual samples from blood test for older patients were evaluated to determine drug metabolism. The body composition of relevant patients was determined by analyzing characteristic parameters of skeletal muscle mass index (SMI), handgrip strength (HGS) and hepatic steatosis index (HSI). The differences in hepatic drug metabolism were studied statistically among categories in terms of the cut-off value of these parameters. RESULTS: Older male patients receiving lansoprazole and nifedipine in the low SMI (<7.0 kg/m² ) category showed an 85-90% reduction in respective CYP2C19 and CYP3A4 metabolic activities compared with the normal SMI category. For the female patients, CYP2C19 and CYP3A4 metabolic activities showed no significant correlation with SMI and HGS. Fatty liver disease (HSI ≥36) was found to reduce CYP2C19 metabolic activity particularly in older female patients. CONCLUSIONS: Low CYP2C19 metabolic activity was statistically correlated with low SMI in male patients and high HSI in female patients, whereas low CYP3A4 metabolic activity was statistically correlated with low HGS in male patients. Geriatr Gerontol Int 2022; 22: 449-454.

Geriatrics & gerontology international published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Related Products of pyridine-derivatives.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Naito, Yasuyuki published the artcileConstructing vascularized hepatic tissue by cell-assembled viscous tissue sedimentation method and its application for vascular toxicity assessment, Safety of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the publication is Acta Biomaterialia (2022), 275-288, database is CAplus and MEDLINE.

In vitro Construction of the liver sinusoidal structure using artificial tissue is an important but worthwhile challenge, particularly for assessing the risk of diseases such as sinusoidal obstruction syndrome (SOS). Current models are unsuitable for evaluating the toxicity because of lacking sinusoidal capillary. In this study, we developed a vascularized hepatic tissue (VHT) using a unique tissue engineering technique, the cell assembled viscous tissue by sedimentation (CAViTs) method. The “viscous bodies” created using the CAViTs method exhibited significant self-assembly within 6 h after seeding, promoting cell-cell interaction. The level of albumin secreted by the VHT was four times higher than that of 2D-coculture and maintained for 1 mo. The gene expression pattern of the VHT was closer to that of total human liver, compared with the 2D system. Quant. evaluations of the vascular structure of VHT treated with two typical SOS-inducing compounds, monocrotaline and retrorsine, revealed higher sensitivity (IC50 = 40.35μM), 19.92 times higher than the cell-viability assay. Thus, VHT represents an innovative in vitro model that mimics the vessel network structure and could become a useful tool for the early screening of compounds associated with a risk of vascular toxicity. Mimicking sinusoidal structures in in vitro liver model is important to consider from the perspective of predicting hepatotoxicity such like sinusoidal obstruction syndrome (SOS). However, it was difficult to reconstruct the vascular structure within the hepatocyte-rich environment. In this study, we constructed a vascularized hepatic tissue in a high-throughput manner by a unique method using collagen and heparin, and evaluated its applicability to toxicity assessment. Vessel morphol. anal. of the model treated by monocrotaline, which is a well-known SOS-inducing compound, could predict the toxicity with higher sensitivity. To the best of our knowledge, this is the first report to provide vascularized hepatic tissues using sinusoidal endothelial cells at least for demonstrating applicability to the evaluation of SOS induction risk.

Acta Biomaterialia published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Safety of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Hong, Bing published the artcileSedimentary spectrum and potential ecological risks of residual pharmaceuticals in relation to sediment-water partitioning and land uses in a watershed, Quality Control of 21829-25-4, the publication is Science of the Total Environment (2022), 152979, database is CAplus and MEDLINE.

Pharmaceutical residues in river surficial sediment are prone to anthropogenic impacts and environmental factors in watershed, but the mechanisms remain unclear. This study attempted to reveal surficial sediment-water pseudo-partitioning and anthropogenic (land use) patterns of pharmaceutical residues in surficial sediment among 23 subwatersheds of Jiulong River, southeast China with a gradient of urban land use percentile in dry and wet seasons. Thirty-eight out of target 86 compounds from six-category pharmaceuticals were quantified and ranged from below the quantification limits (0.001 mg kg^-1 dry mass) up to 8.19 mg kg^-1 dry mass (chlortetracycline) using a developed SPE-HPLC-MS/MS protocol. Antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) collectively dominated sedimentary pharmaceutical residues for 34.5-99.8% of the total quantified compounds (median at 92%). Land uses in subwatersheds showed high consistency with sedimentary pharmaceutical residues in the dry season rather than the wet season, especially for human use only and veterinary use only compounds Surficial sediment-water partitioning of pharmaceutical compounds influenced their sedimentary residues regardless of season, which were determined by properties of compound and surficial sediment interactively. All tetracycline compounds, trimethoprim (sulfonamides synergist), caffeine (central nervous system drug), and oxfendazole (antiparasitic drug) were quantified to pose high potential ecol. risks to aquatics. Findings of this study suggest that pseudo-persistent legacy of human and veterinary pharmaceuticals requires a wider coverage of pharmaceutical compounds for a comprehensive ecol. assessment in the environment and more involvement of anthropogenic impacts and socioeconomic factors in the future studies.

Science of the Total Environment published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Quality Control of 21829-25-4.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Motomura, Naoki published the artcileVisualization of calcium channel blockers in human adrenal tissues and their possible effects on steroidogenesis in the patients with primary aldosteronism (PA), Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the publication is Journal of Steroid Biochemistry and Molecular Biology (2022), 106062, database is CAplus and MEDLINE.

Voltage-gated L-type calcium channel (CaV) isoforms are well known to play pivotal tissue-specific roles not only in vasoconstriction but also in adrenocortical steroidogenesis including aldosterone biosynthesis. Alpha-1C subunit calcium channel (CC) (CaV1.2) is the specific target of anti-hypertensive CC blockers (CCBs) and its Alpha-1D subunit (CaV1.3) regulates depolarization of cell membrane in aldosterone-producing cells. Direct effects of CCBs on aldosterone biosynthesis were previously postulated but their intra-adrenal distribution and effects on steroid production in primary aldosteronism (PA) patients have remained virtually unknown. In this study, frozen tissue specimens constituting tumor, adjacent adrenal gland and peri-adrenal adipose tissues of nine aldosterone-producing adenoma (APA) cases were examined for visualization of amlodipine and aldosterone themselves using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Liquid chromatog.-mass spectrometry (LC-MS) anal. was also performed to quantify amlodipine and 17 adrenal steroids in those cases above and compared the findings with immunohistochem. anal. of steroidogenic enzymes and calcium channels (CaV1.2 and CaV1.3). Effects of amlodipine on mRNA level of aldosterone biosynthetic enzymes were also explored using human adrenocortical carcinoma cell line (H295R). Amlodipine-specific peak (m/z 407.1 > 318.1) was detected only in amlodipine treated cases. Accumulation of amlodipine was marked in adrenal cortex compared to peri-adrenal adipose tissues but not significantly different between APA tumors and adjacent adrenal glands, which was subsequently confirmed by LC-MS quantification. Intra-adrenal distribution of amlodipine was generally consistent with that of CCs. In addition, quant. steroid profiles using LC-MS and in vitro study demonstrated the lower HSD3B activities in amlodipine treated cases. Immunoreactivity of CaV1.2 and HSD3B2 were also correlated. We report the first demonstration of specific visualization of amlodipine in human adrenal tissues by MALDI-MSI. Marked amlodipine accumulation in the adrenal glands suggested its direct effects on steroidogenesis in PA patients, possibly targeting on CaV1.2 and suppressing HSD3B activity.

Journal of Steroid Biochemistry and Molecular Biology published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Jahed, Zeinab published the artcileNanocrown electrodes for parallel and robust intracellular recording of cardiomyocytes, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the publication is Nature Communications (2022), 13(1), 2253, database is CAplus and MEDLINE.

Drug-induced cardiotoxicity arises primarily when a compound alters the electrophysiol. properties of cardiomyocytes. Features of intracellular action potentials (iAPs) are powerful biomarkers that predict proarrhythmic risks. In the last decade, a number of vertical nanoelectrodes have been demonstrated to achieve parallel and minimally-invasive iAP recordings. However, the large variability in success rate and signal strength have hindered nanoelectrodes from being broadly adopted for proarrhythmia drug assessment. In this work, we develop vertically-aligned nanocrown electrodes that are mech. robust and achieve > 99% success rates in obtaining intracellular access through electroporation. We validate the accuracy of nanocrown electrode recordings by simultaneous patch clamp recording from the same cell. Finally, we demonstrate that nanocrown electrodes enable prolonged iAP recording for continual monitoring of the same cells upon the sequential addition of four incremental drug doses. Our technol. development provides an advancement towards establishing an iAP screening assay for preclin. evaluation of drug-induced arrhythmogenicity.

Nature Communications published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Yu, Weiqun published the artcileReviving Cav1.2 as an attractive drug target to treat bladder dysfunction, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the publication is FASEB Journal (2022), 36(1), e22118, database is CAplus and MEDLINE.

A review. Inhibition of bladder contraction with antimuscarinics is a common approach to treat bladder hyperactivity, and the L-type voltage-gated calcium channel α1C (Cav1.2) is crucial for bladder contractility. Therefore, strategies aimed at inhibiting Cav1.2 appear warranted. However, multiple clin. trials that attempted to treat bladder overactivity with calcium channel blockers (CCBs) have been unsuccessful, creating an unsolved mystery. In contrast, cardiologists and epidemiologists have reported strong associations between CCB use and bladder hyperactivity, opposing expectations of urologists. Recent findings from our lab offer a potential explanation. We have demonstrated that ketamine which can cause cystitis, functions, like nifedipine, as a Cav1.2 antagonist. We also show that a Cav1.2 agonist which potentiates muscle contraction, rather than antagonizing it, can increase the volume of voids and reduce voiding frequency. This perspective will discuss in detail the unsuccessful urol. trials of CCBs and the promise of Cav1.2 agonists as potential novel therapies for bladder dysfunctions.

FASEB Journal published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C16H20N2, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Christophe, Bernard published the artcileOccurrence of early after depolarization under healthy or hypertrophic cardiomyopathy conditions in the human ventricular endocardial myocyte: In silico study using 109 torsadogenic or non-torsadogenic compounds, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the publication is Toxicology and Applied Pharmacology (2022), 115914, database is CAplus and MEDLINE.

The goal of the CiPA initiative (Comprehensive in vitro Proarrhythmia Assay) was to assess a more accurate prediction of new drug candidate proarrhythmic severe liabilities such as torsades de pointes, for example. This new CiPA paradigm was partly based on in silico reconstruction of human ventricular cardiomyocyte action potential useful to identify repolarization abnormalities such early afterdepolarization (EAD), for example. Using the ToR-ORd algorithm (Tomek-Rodriguez-O’Hara-Rudy dynamic model), the aim of the present work was (i) to identify intracellular parameters leading to EAD occurrence under healthy and hypertrophic cardiomyopathy (HCM) conditions and (ii) to evaluate the prediction accuracy of compound torsadogenic risk based on EAD occurrence using a large set of 109 torsadogenic and non-torsadogenic compounds under both exptl. conditions. In silico results highlighted the crucial involvement of Ca++ handling in the ventricular cardiomyocyte intracellular subspace compartment for the initiation of EAD, demonstrated by a higher amplitude of Ca++ release from junctional sarcoplasmic reticulum to subspace compartments (Jrel) measured at EAD take-off voltage in the presence vs. the absence of EAD initiated either by high IKr inhibition or by high enough concentration of a torsadogenic compound under both exptl. conditions. Under healthy or HCM conditions, the prediction accuracy of the torsadogenic risk of compound based on EAD occurrence was observed to be 61 or 92%, resp. This high accuracy under HCM conditions was discussed regarding its usefulness for cardiac safety pharmacol. at least at early drug screening/preclin. stage of the drug development process.

Toxicology and Applied Pharmacology published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Wang, Pengfei published the artcileThe fingerprints of nifedipine/isonicotinamide cocrystal polymorph studied by terahertz time-domain spectroscopy, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the publication is International Journal of Pharmaceutics (Amsterdam, Netherlands) (2022), 121759, database is CAplus and MEDLINE.

Cocrystal is constructed to improve physicochem. properties of active pharmaceutical ingredient and prevent polymorphism via intermol. interactions. However, recent examples on cocrystal polymorphs display significantly different properties. Even though some anal. techniques have been used to characterize the cocrystal polymorphic system, it remains unclear how intermol. interactions drive and stabilize the structure. In this work, we study the cocrystal polymorphs of nifedipine (NFD) and isonicotinamide (INA) using terahertz (THz) spectroscopy. Form I and form II of NFD-INA cocrystals show spectral fingerprints in THz region. Temperature-dependent THz spectra display distinguished frequency shifts of each fingerprint. Combined with solid-state d. functional theory (DFT) calculations, the exptl. fingerprints and their distinct responses to temperature are elucidated by specific collective vibrational modes. The vibrations of hydrogen bonding between dihydropyridine ring of NFD and INA are generally distributed below 1.5 THz, which play important roles in stabilizing cocrystal and preventing the oxidation of NFD. The rotations of Me group in NFD are widely distributed in the range of 1.5-4.0 THz, which helps the steric recognition. The results demonstrate that THz spectroscopy is a sensitive tool to discriminate cocrystal polymorphs. It has the potential to be used as a non-invasive technique for pharmaceutical screening.

International Journal of Pharmaceutics (Amsterdam, Netherlands) published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C19H14Cl2, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Zhang, Yi-Lin published the artcileCellular mechanism underlying the facilitation of contractile response induced by tumor necrosis factor-α in mouse tracheal smooth muscle, Product Details of C17H18N2O6, the publication is American Journal of Pathology (2022), 192(1), 104-111, database is CAplus and MEDLINE.

The proinflammatory cytokine tumor necrosis factor-α (TNF-α) augments intracellular Ca2+ signaling and contractile responses of airway smooth muscles, leading to airway hyperresponsiveness. However, the underlying mechanism has not been fully elucidated. This study aimed to investigate the cellular mechanism of the potentiated contraction of mouse tracheal smooth muscle induced by TNF-α. The results showed that TNF-α triggered facilitation of mouse tracheal smooth muscle contraction in an epithelium-independent manner. The TNF-α-induced hypercontractility could be suppressed by the protein kinase C inhibitor GF109203X, the tyrosine kinase inhibitor genistein, the Src inhibitor PP2, or the L-type voltage-dependent Ca2+ channel blocker nifedipine. Following TNF-α incubation, the α1C L-type Ca2+ channel (CaV1.2) was up-regulated in cultured primary mouse tracheal smooth muscle cells. Pronounced phosphotyrosine levels were observed in mouse tracheas. In conclusion, this study shows that TNF-α enhanced airway smooth muscle contraction via protein kinase C-Src-CaV1.2 pathways, which provides novel insights into the pathol. role of proinflammatory cytokines in mediating airway hyperresponsiveness.

American Journal of Pathology published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C14H10O4S2, Product Details of C17H18N2O6.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem