Category: 21829-25-4

Andrews, L. M. published the artcileA population pharmacokinetic model to predict the individual starting dose of tacrolimus in adult renal transplant recipients, Related Products of pyridine-derivatives, the main research area is tacrolimus renoprotectant CYP3A4 albumin kidney transplantation adult; cytochrome P450 enzymes; genetics and pharmacogenetics; immunosuppression Immunology; pharmacokinetics; population analysis; renal transplantation.

To describe the pharmacokinetics of tacrolimus immediately after kidney transplantation, and to develop a clin. tool for selecting the best starting dose for each patient. Data on tacrolimus exposure were collected for the first 3 mo following renal transplantation. A population pharmacokinetic anal. was conducted using nonlinear mixed-effects modeling. Demog., clin. and genetic parameters were evaluated as covariates. A total of 4527 tacrolimus blood samples collected from 337 kidney transplant recipients were available. Data were best described using a two-compartment model. The mean absorption rate was 3.6 h-1, clearance was 23.0 l h-1 (39% interindividual variability, IIV), central volume of distribution was 692 l (49% IIV) and the peripheral volume of distribution 5340 l (53% IIV). Interoccasion variability was added to clearance (14%). Higher body surface area (BSA), lower serum creatinine, younger age, higher albumin and lower haematocrit levels were identified as covariates enhancing tacrolimus clearance. Cytochrome P 450 (CYP) 3A5 expressers had a significantly higher tacrolimus clearance (160%), whereas CYP3A4*22 carriers had a significantly lower clearance (80%). From these significant covariates, age, BSA, CYP3A4 and CYP3A5 genotype were incorporated in a second model to individualize the tacrolimus starting dose: Dosemg=222nghml-1*22.5lh-1*1.0ifCYP3A5*3/*3or1.62ifCYP3A5*1/*3orCYP3A5*1/*1*1.0ifCYP3A4*1or unknownor0.814ifCYP3A4*22*Age56-0.50*BSA1.930.72/1000 Both models were successfully internally and externally validated. A clin. trial was simulated to demonstrate the added value of the starting dose model. For a good prediction of tacrolimus pharmacokinetics, age, BSA, CYP3A4 and CYP3A5 genotype are important covariates. These covariates explained 30% of the variability in CL/F. The model proved effective in calculating the optimal tacrolimus dose based on these parameters and can be used to individualize the tacrolimus dose in the early period after transplantation.

British Journal of Clinical Pharmacology published new progress about Adult, mammalian. 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, Related Products of pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Mao, Junjun published the artcileIncorporating nonlinear kinetics to improve predictive performance of population pharmacokinetic models for ciclosporin in adult renal transplant recipients: A comparison of modelling strategies, Related Products of pyridine-derivatives, the main research area is ciclosporin renoprotectant pharmacokinetic renal transplantation; Ciclosporin; Modelling strategies; Nonlinear kinetics; Population pharmacokinetics.

Ciclosporin has been shown to follow nonlinear pharmacokinetics (PK) in renal transplant recipients who received ciclosporin (Neoral, Novartis)-based triple immunosuppressive therapy. Some of these nonlinear properties have not been fully considered in population PK (popPK) anal. Therefore, the aim of this study was to determine the potential influence of nonlinearity and the functional forms of covariates on model predictability as well as to analyze multiple nonlinear factors in the in vivo process. A total of 2969 ciclosporin whole-blood measurements, including 1328 pre-dose and 1641 2-h post-dose concentrations, were collected from 173 patients who underwent their first renal transplantation. Four popPK models based on different modeling strategies were developed to investigate the discrepancy between empirical and theory-based, linear and nonlinear compartmental kinetic models and empirical formulas on model predictability. Prediction and simulation-based diagnostics (prediction-corrected visual predictive checks) were performed to determine the stability and predictive performance of these four models. Model predictability improved when nonlinearity was considered. The theory-based nonlinear model which incorporated nonlinear property based on known theor. relationships performed better than the other two compartmental models. The nonlinear Michaelis-Menten model showed a remarkable improvement in predictive performance compared to the other three compartmental models. The saturated binding of ciclosporin to erythrocytes, auto-inhibition induced by the inhibitory effects of ciclosporin on cytochrome P 450 3A4/P-glycoprotein may have contributed to the nonlinearity. Ciclosporin-prednisolone drug interaction should be given serious consideration in clin. settings. Incorporation of nonlinear properties is likely to be a promising approach for improving ciclosporin model predictability. Theory-based modeling is helpful to improve model predictability. However, ciclosporin nonlinear kinetics resources need further investigation.

European Journal of Pharmaceutical Sciences published new progress about Adult, mammalian. 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, Related Products of pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Giantin, Mery published the artcileFunctional impact of cytochrome P450 3A (CYP3A) missense variants in cattle, Formula: C17H18N2O6, the main research area is CYPA missense mutation testosterone nifedipine mol docking.

Cytochrome P 450 3A is the most important CYP subfamily in humans, and CYP3A4/CYP3A5 genetic variants contribute to inter-individual variability in drug metabolism However, no information is available for bovine CYP3A (bCYP3A). Here we described bCYP3A missense single nucleotide variants (SNVs) and evaluated their functional effects. CYP3A28, CYP3A38 and CYP3A48 missense SNVs were identified in 300 bulls of Piedmontese breed through targeted sequencing. Wild-type and mutant bCYP3A cDNAs were cloned and expressed in V79 cells. CYP3A-dependent oxidative metabolism of testosterone (TST) and nifedipine (NIF) was assessed by LC-MS/MS. Finally, SNVs functional impact on TST hydroxylation was measured ex vivo in liver microsomes from individually genotyped animals. Thirteen missense SNVs were identified and validated. Five variants showed differences in CYP3A catalytic activity: three CYP3A28 SNVs reduced TST 6β-hydroxylation; one CYP3A38 variant increased TST 16β-hydroxylation, while a CYP3A48 SNV showed enhanced NIF oxidation Individuals homozygous for rs384467435 SNV showed a reduced TST 6β-hydroxylation. Mol. modeling showed that most of SNVs were distal to CYP3A active site, suggesting indirect effects on the catalytic activity. Collectively, these findings demonstrate the importance of pharmacogenetics studies in veterinary species and suggest bCYP3A genotype variation might affect the fate of xenobiotics in food-producing species such as cattle.

Scientific Reports published new progress about Allele frequency. 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, Formula: C17H18N2O6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Yang, Yilei published the artcileCYP3A5 genotype-dependent drug-drug interaction between tacrolimus and nifedipine in Chinese renal transplant patients, Category: pyridine-derivatives, the main research area is tacrolimus nifedipine human renal transplant CYP3A5 genotype drug interaction; CYP3A5; drug-drug interaction; nifedipine; renal transplantation; tacrolimus.

The drug-drug interactions (DDIs) of tacrolimus greatly contributed to pharmacokinetic variability. Nifedipine, frequently prescribed for hypertension, is a competitive CYP3A5 inhibitor which can inhibit tacrolimus metabolism The objective of this study was to investigate whether CYP3A5 genotype could influence tacrolimusnifedipine DDI in Chinese renal transplant patients. All renal transplant patients were divided into CYP3A5*3/*3 homozygotes (group I) and CYP3A5*1 allele carriers (CYP3A5*1/*1 + CYP3A5*1/*3) (group II). Each group was subdivided into patients taking tacrolimus co-administered with nifedipine (CONF) and that administrated with tacrolimus alone (Controls). Tacrolimus trough concentrations (C0) were measured using high performance liquid chromatog. A retrospective anal. compared tacrolimus dose (D)-corrected trough concentrations (C0) (C0/D) between CONF and Controls in group I and II, resp. At the same time, a multivariate line regression anal. was made to evaluate the effect of variates on C0/D. In this study, a significant DDI between tacrolimus and nifedipine with respect to the CYP3A5*3 polymorphism was confirmed. In group I (n = 43), the C0/D of CONF was significantly higher than in Controls [225.2 ± 66.3 vs. 155.1 ± 34.6 ng/mL/(mg/kg); p = 0.002]. However, this difference was not detected in group II (n = 27) (p = 0.216). The coadministrated nifedipine and CYP3A5*3/*3 homozygotes significantly increased tacrolimus concentrations in multivariate line regression anal. A CYP3A5 genotype-dependent DDI was found between tacrolimus and nifedipine. Therefore, personalized therapy accounting for CYP3A5 genotype detection as well as therapeutic drug monitoring are necessary for renal transplant patients when treating with tacrolimus and nifedipine.

Frontiers in Pharmacology published new progress about Allele frequency. 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, Category: pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Jiang, Lin published the artcileCRISPR activation of endogenous genes reprograms fibroblasts into cardiovascular progenitor cells for myocardial infarction therapy, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the publication is Molecular Therapy (2022), 30(1), 54-74, database is CAplus and MEDLINE.

Fibroblasts can be reprogrammed into cardiovascular progenitor cells (CPCs) using transgenic approaches, although the underlying mechanism remains unclear. We determined whether activation of endogenous genes such as Gata4, Nkx2.5, and Tbx5 can rapidly establish autoregulatory loops and initiate CPC generation in adult extracardiac fibroblasts using a CRISPR activation system. The induced fibroblasts (>80%) showed phenotypic changes as indicated by an Nkx2.5 cardiac enhancer reporter. The progenitor characteristics were confirmed by colony formation and expression of cardiovascular genes. Cardiac sphere induction segregated the early and late reprogrammed cells that can generate functional cardiomyocytes and vascular cells in vitro. Therefore, they were termed CRISPR-induced CPCs (ciCPCs). Transcriptomic anal. showed that cell cycle and heart development pathways were important to accelerate CPC formation during the early reprogramming stage. The CRISPR system opened the silenced chromatin locus, thereby allowing transcriptional factors to access their own promoters and eventually forming a pos. feedback loop. The regenerative potential of ciCPCs was assessed after implantation in mouse myocardial infarction models. The engrafted ciCPCs differentiated into cardiovascular cells in vivo but also significantly improved contractile function and scar formation. In conclusion, multiplex gene activation was sufficient to drive CPC reprogramming, providing a new cell source for regenerative therapeutics.

Molecular Therapy 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, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

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

Tung, Ying-Chang published the artcileComparative effectiveness of generic nifedipine versus Adalat long-acting nifedipine for hypertension treatment: A multi-institutional cohort study, Product Details of C17H18N2O6, the publication is Journal of Clinical Hypertension (Hoboken, NJ, United States) (2022), 24(5), 621-629, database is CAplus and MEDLINE.

This retrospective multi-institutional database anal. aimed to evaluate the blood-pressure-lowering efficacy and clin. outcomes of a generic vs. brand-name nifedipine for hypertension management. A total of 12 693 patients who were prescribed a generic or brand-name nifedipine between Jan. 1, 2011, and Dec. 31, 2018, were identified from the Chang Gung Research Database of Chang Gung Memorial Hospitals, Taiwan. Among them, 2112 (21.4%) were prescribed generic nifedipine. After propensity score matching, both the generic and brand-name groups consisted of 2102 patients. At a mean follow-up of 3 years, the changes in office systolic (p for interaction = .791) and diastolic blood pressure (p for interaction = .689) did not differ significantly between the patients who received the generic and the brand-name nifedipine. There was no significant difference between the two study groups regarding the composite of all-cause mortality, acute myocardial infarction, stroke, coronary revascularization, or hospitalization for heart failure (hazard ratio 0.98, 95% confidence interval 0.85-1.13; p = .774). In conclusion, the generic nifedipine was comparable to its brand-name counterpart regarding office blood pressure reduction and the composite cardiovascular outcome for the treatment of patients with hypertension.

Journal of Clinical Hypertension (Hoboken, NJ, United States) 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 C6H6BClO3, Product Details of C17H18N2O6.

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

Bertagna, Federico published the artcileThapsigargin blocks electromagnetic field-elicited intracellular Ca²⁺ increase in HEK 293 cells, Computed Properties of 21829-25-4, the publication is Physiological Reports (2022), 10(9), e15189, database is CAplus and MEDLINE.

Biol. effects of electromagnetic fields (EMFs) have previously been identified for cellular proliferation and changes in expression and conduction of diverse types of ion channels. The major effect elicited by EMFs seems to be directed toward Ca2+ homeostasis. This is particularly remarkable since Ca2+ acts as a central modulator in various signaling pathways, including, but not limited to, cell differentiation and survival. Despite this, the mechanisms underlying this modulation have yet to be unraveled. Here, we assessed the effect of EMFs on intracellular [Ca2+], by exposing HEK 293 cells to both radio-frequency electromagnetic fields (RF-EMFs) and static magnetic fields (SMFs). We detected a constant and significant increase in [Ca2+] subsequent to exposure to both types of fields. Strikingly, the increase was nulled by administration of 10 μM Thapsigargin, a blocker of sarco/endoplasmic reticulum Ca2+-ATPases (SERCAs), indicating the involvement of the endoplasmic reticulum (ER) in EMF-related modulation of Ca2+ homeostasis.

Physiological Reports 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, Computed Properties of 21829-25-4.

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

Li, Shikai published the artcileInhibition of Sympathetic Activation by Delivering Calcium Channel Blockers from a 3D Printed Scaffold to Promote Bone Defect Repair, Related Products of pyridine-derivatives, the publication is Advanced Healthcare Materials (2022), 11(16), 2200785, database is CAplus and MEDLINE.

Enhancing osteogenesis by promoting neural network reconstruction and neuropeptide release is considered to be an attractive strategy for repairing of critical size bone defects. However, traumatic bone defects often activate the damaged sympathetic nervous system (SNS) in the defect area and release excessive catecholamine to hinder bone defect repair. Herein, a 3D printed scaffold loaded with the calcium channel blocker-nifedipine is proposed to reduce the concentration of catecholamine present in the bone defect region and to accelerate bone healing. To this end, nifedipine-loaded ethosome and laponite are added into a mixed solution containing sodium alginate, methacrylated gelatin, and bone mesenchymal stem cells (BMSCs) to prepare a cell-laden scaffold using 3D bioprinting. The released nifedipine is able to close the calcium channels of nerve cells, thereby blocking sympathetic activation and ultimately inhibiting the release of catecholamine by sympathetic nerve cells, which further promotes the osteogenic differentiation and migration of BMSCs, inhibits osteoclastogenesis in vitro, and effectively improves bone regeneration in a rat critical-size calvarial defect model. Therefore, the results suggest that sustained release of nifedipine from the scaffold can effectively block SNS activation, providing promising strategies for future treatment of bone defects.

Advanced Healthcare Materials 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

Yang, Biao published the artcileA conductive supramolecular hydrogel creates ideal endogenous niches to promote spinal cord injury repair, Product Details of C17H18N2O6, the publication is Bioactive Materials (2022), 103-119, database is CAplus and MEDLINE.

The current effective method for treatment of spinal cord injury (SCI) is to reconstruct the biol. microenvironment by filling the injured cavity area and increasing neuronal differentiation of neural stem cells (NSCs) to repair SCI. However, the method is characterized by several challenges including irregular wounds, and mech. and elec. mismatch of the material-tissue interface. In the current study, a unique and facile agarose/gelatin/polypyrrole (Aga/Gel/PPy, AGP3) hydrogel with similar conductivity and modulus as the spinal cord was developed by altering the concentration of Aga and PPy. The gelation occurred through non-covalent interactions, and the phys. crosslinked features made the AGP3 hydrogels injectable. In vitro cultures showed that AGP3 hydrogel exhibited excellent biocompatibility, and promoted differentiation of NSCs toward neurons whereas it inhibited over-proliferation of astrocytes. The in vivo implanted AGP3 hydrogel completely covered the tissue defects and reduced injured cavity areas. In vivo studies further showed that the AGP3 hydrogel provided a biocompatible microenvironment for promoting endogenous neurogenesis rather than glial fibrosis formation, resulting in significant functional recovery. RNA sequencing anal. further indicated that AGP3 hydrogel significantly modulated expression of neurogenesis-related genes through intracellular Ca2+ signaling cascades. Overall, this supramol. strategy produces AGP3 hydrogel that can be used as favorable biomaterials for SCI repair by filling the cavity and imitating the physiol. properties of the spinal cord.

Bioactive Materials 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 C9H11BO4, Product Details of C17H18N2O6.

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

Ulivieri, Alessandra published the artcileThyroid hormones regulate cardiac repolarization and QT-interval related gene expression in hiPSC cardiomyocytes, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the publication is Scientific Reports (2022), 12(1), 568, database is CAplus and MEDLINE.

Prolongation of cardiac repolarization (QT interval) represents a dangerous and potentially life-threatening elec. event affecting the heart. Thyroid hormones (THs) are critical for cardiac development and heart function. However, little is known about THs influence on ventricular repolarization and controversial effects on QT prolongation are reported. Human iPSC-derived cardiomyocytes (hiPSC-CMs) and multielectrode array (MEA) systems were used to investigate the influence of 3,3′,5-triiodo-L-Thyronine (T3) and 3,3′,5,5′-tetraiodo-L-Thyronine (T4) on corrected Field Potential Duration (FPDc), the in vitro analog of QT interval, and on local extracellular Action Potential Duration (APD). Treatment with high THs doses induces a significant prolongation of both FPDc and APD, with the strongest increase reached after 24 h exposure. Preincubation with reverse T3 (rT3), a specific antagonist for nuclear TH receptor binding, significantly reduces T3 effects on FPDc, suggesting a TRs-mediated transcriptional mechanism. RNA-seq anal. showed significant deregulation in genes involved in cardiac repolarization pathways, including several QT-interval related genes. In conclusion, long-time administration of high THs doses induces FPDc prolongation in hiPSC-CMs probably through the modulation of genes linked to QT-interval regulation. These results open the way to investigate new potential diagnostic biomarkers and specific targeted therapies for cardiac repolarization dysfunctions.

Scientific Reports 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 C9H5Cl2F3, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

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