Tag: M.W=200-350

Utsey, Kiersten published the artcileQuantification of the impact of partition coefficient prediction methods on physiologically based pharmacokinetic model output using a standardized tissue composition, Computed Properties of 21829-25-4, the main research area is partition coefficient prediction physiol pharmacokinetic model standardized tissue composition.

Tissue:plasma partition coefficients are key parameters in physiol. based pharmacokinetic (PBPK) models, yet the coefficients are challenging to measure in vivo. Several mechanistic-based equations have been developed to predict partition coefficients using tissue composition information and the compound’s physicochem. properties, but it is not clear which, if any, of the methods is most appropriate under given circumstances. Complicating the evaluation, each prediction method was developed, and is typically employed, using a different set of tissue composition information, thereby making a controlled comparison impossible. This study proposed a standardized tissue composition for humans that can be used as a common input for each of the five frequently used prediction methods. These methods were implemented in R and were used to predict partition coefficients for 11 drugs, classified as strong bases, weak bases, acids, neutrals, and zwitterions. PBPK models developed in R (mrgsolve) for each drug and each set of partition coefficient predictions were compared with resp. observed plasma concentration data. Percent root mean square error and half-life percent error were used to evaluate the accuracy of the PBPK model predictions using each partition coefficient method as summarized by strong bases, weak bases, acids, neutrals, and zwitterions characterization. The anal. indicated that no partition coefficient method consistently yielded the most accurate PBPK model predictions. As such, PBPK model predictions using all partition coefficient methods should be considered during drug development.

Drug Metabolism & Disposition published new progress about Adipocyte. 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, Computed Properties of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Yastrebova, Ekaterina S. published the artcileProposed Dynamics of CDB3 Activation in Human Erythrocytes by Nifedipine Studied with Scanning Flow Cytometry, Formula: C17H18N2O6, the main research area is nifedipine erythrocyte CDB3 flow cytometry; adalat; band 3; calcium ions; kinetic modeling; red blood cells.

Nifedipine is calcium channels and pumps blocker widely used in medicine. However, mechanisms of nifedipine action in blood are not clear. In particular, the influence of nifedipine on erythrocytes is far from completely understood. In this work, applying scanning flow cytometry, we observed exptl. for the first time the dynamics behind a significant increase of HCO3-/Cl- transmembrane exchange rate of CDB3 (main anion exchanger, AE1, Band 3, SLC4A1) of human erythrocytes in the presence of nifedipine in blood. It was found that the rate of CDB3 activation is not limited by the rate of nifedipine binding and/or Ca2+ transport. In order to explain the exptl. data, we suggested a kinetic model assuming that the rate of CDB3 activation is limited by the dynamics of the balance between two intracellular processes (1) the activation of CDB3 limited by its interaction with intracellular Ca2+, and (2) the spontaneous deactivation of CDB3.

Cytometry, Part A published new progress about Algorithm. 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

Seibertz, Fitzwilliam published the artcileSingle-cell optical action potential measurement in human induced pluripotent stem cell-derived cardiomyocytes, Related Products of pyridine-derivatives, the main research area is singlecell optical action potential human pluripotent stem cell cardiomyocyte.

Conventional intracellular microelectrode techniques to quantify cardiomyocyte electrophysiol. are extremely complex, labor intensive, and typically carried out in low throughput. Rapid and ongoing expansion of induced pluripotent stem cell (iPSC) technol. presents a new standard in cardiovascular research and alternate methods are now necessary to increase throughput of electrophysiol. data at a single cell level. VF2.1Cl is a recently derived voltage sensitive dye which provides a rapid single channel, high magnitude response to fluctuations in membrane potential. It possesses kinetics superior to those of other existing voltage indicators and makes available functional data equivalent to that of traditional microelectrode techniques. Here, we demonstrate simplified, non-invasive action potential characterization in externally paced human iPSC derived cardiomyocytes using a modular and highly affordable photometry system.

Journal of Visualized Experiments published new progress about Absorption. 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

Bi, Ye published the artcileA liposomal formulation for improving solubility and oral bioavailability of nifedipine, COA of Formula: C17H18N2O6, the main research area is nifedipine liposome oral drug delivery formulation controlled release bioavailability; bioavailability; nifedipine; pharmacokinetics; proliposomes.

Proliposomes were used to improve the solubility and oral bioavailability of nifedipine. Nifedipine proliposomes were prepared by methanol injection-spray drying method. The response surface method was used to optimize formulation to enhance the encapsulation efficiency (EE%) of nifedipine. The particle size of nifedipine proliposomes after rehydration was 114 nm. Surface morphol. of nifedipine proliposomes was observed by a scanning electron microscope (SEM) and interaction of formulation ingredients was assessed by differential scanning calorimetry (DSC). The solubility of nifedipine is improved 24.8 times after forming proliposomes. In vitro release experiment, nifedipine proliposomes had a control release effect, especially in simulated gastric fluid. In vivo, nifedipine proliposomes significantly improved the bioavailability of nifedipine. The area under the concentration-time curve (AUC0-âˆ? of nifedipine proliposomes was about 10 times than nifedipine after oral administration. The elimination half-life (T1/2β) of nifedipine was increased from 1.6 h to 6.6 h. In conclusion, proliposomes was a promising system to deliver nifedipine through oral route and warranted further investigation.

Molecules published new progress about Absorption. 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, COA of Formula: C17H18N2O6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Nakanishi, Atsushi published the artcileSpectral imaging of pharmaceutical materials with a compact terahertz difference-frequency generation semiconductor source, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is pharmaceutical material spectral imaging terahertz frequency generation semiconductor.

Spectral imaging of pharmaceutical material using a compact ultra-broadband (1-4 THz) terahertz semiconductor source was demonstrated. False-color RGB images could be obtained using a simple procedure (calibration free). The ability to distinguish the polymorphism of carbamazepine (CBZ), the hydrate forms of D-(+)-glucose and caffeine, and the crystallinity of nifedipine was demonstrated using the THz DFG source. Crystal forms of pharmaceutical materials can be distinguished using this method.

Analytical Methods published new progress about Absorption. 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, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Tubtimsri, Sukannika published the artcileImprovement in Solubility and Absorption of Nifedipine Using Solid Solution: Correlations between Surface Free Energy and Drug Dissolution, COA of Formula: C17H18N2O6, the main research area is nifedipine absorption solubility surface free energy drug dissolution correlation; nifedipine; polysorbate; poorly water-soluble drug; solid solution; third generation solid dispersion.

Ternary solid solutions composed of nifedipine (NDP), amino methacrylate copolymer (AMCP), and polysorbate (PS) 20, 60, or 65 were prepared using a solvent evaporation method. The dissolution profiles of NDP were used to study the effect of the addition of polysorbate based on hydrophilic properties. A solid solution of NDP and AMCP was recently developed; however, the dissolution of NDP was <70%. In the present study, polysorbate was added to improve the dissolution of the drug by altering its hydrophilicity. The suitable formulation contained NDP and AMCP at a ratio of 1:4 and polysorbate at a concentration of 0.1%, 0.3%, or 0.6%. Differential scanning calorimetry and powder X-ray diffraction were used to examine the solid solutions No peak representing crystalline NDP was observed in any solid solution samples, suggesting that the drug was molecularly dispersed in AMCP. The NDP dissolution from NDP powder and solid solution without PS were 16.82% and 58.19%, resp. The highest dissolution of NDP of approx. 95.25% was noted at 120 min for the formulation containing 0.6% PS20. Linear correlations were observed between the surface free energy and percentages of dissolved NDP (R2 = 0.7115-0.9315). Cellular uptake across Caco-2 was selected to determine the drug permeability. The percentages of cellular uptake from the NDP powder, solid solution without and with PS20 were 0.25%, 3.60%, and 7.27%, resp. Polymers (Basel, Switzerland) published new progress about Absorption. 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, COA of Formula: C17H18N2O6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Ismail, Mai S. published the artcileDevelopment and assessment of oral nifedipine colloidal provesicles, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is review nifedipine colloidal provesicle assessment development.

Nifedipine(NIF), a well-known calcium channel blocker, is used in the management of hypertension especially if concomitant with kidney, heart or hormonal disorders in children. Colloidal vesicular systems were reported to improve oral absorption and bioavailability of hydrophobic drugs, so the current work embodies a new type of liquid oral colloidal provesicular nano-carrier of NIF. It was developed by simple slurry method. The optimum composition of appropriate lipid film, the effect of surfactant HLB values and cholesterol level on the entrapment efficiency of NIF within liberated vesicles were studied. Addnl., investigating the effect of both initial amount of NIF and the total lipid contents on NIF vesicular entrapment and drug loading were assessed. The morphol. and particle size of both provesicles and liberated nano-vesicles were estimated microscopically and by TEM. The study revealed that 300μmol total lipids of Span 20 /cholesterol at (9:1) molar ratio is an optimum lipid film for higher NIF encapsulation. The vesicular size attained was 209 nm and 79% EE. The in-vitro release study at pH 6.8 revealed an extended release pattern controlling both the release rate and extent. Furthermore, The DSC study showed The successful of intercalating NIF within the vesicle bilayer. This indicate the ability of these provesicles to load NIF successfully.

World Journal of Pharmacy and Pharmaceutical Sciences published new progress about Absorption. 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

Hu, H. published the artcileEngineering of a spider peptide via conserved structure-function traits optimizes sodium channel inhibition in vitro and anti-nociception in vivo, SDS of cas: 21829-25-4, the main research area is spider peptide conserved structure function sodium channel inhibition antinociception; chronic pain; neurological diseases; optimization; peptide engineering; rational design; sodium channel; spider peptide; therapy.

Venom peptides are potent and selective modulators of voltage-gated ion channels that regulate neuronal function both in health and in disease. We previously identified the spider venom peptide Tap1a from the Venezuelan tarantula Theraphosa apophysis that targeted multiple voltage-gated sodium and calcium channels in visceral pain pathways and inhibited visceral mechano-sensing neurons contributing to irritable bowel syndrome. In this work, alanine scanning and domain activity anal. revealed Tap1a inhibited sodium channels by binding with nanomolar affinity to the voltage-sensor domain II utilizing conserved structure-function features characteristic of spider peptides belonging to family NaSpTx1. In order to speed up the development of optimized NaV-targeting peptides with greater inhibitory potency and enhanced in vivo activity, we tested the hypothesis that incorporating residues identified from other optimized NaSpTx1 peptides into Tap1a could also optimize its potency for NaVs. Applying this approach, we designed the peptides Tap1a-OPT1 and Tap1a-OPT2 exhibiting significant increased potency for NaV1.1, NaV1.2, NaV1.3, NaV1.6 and NaV1.7 involved in several neurol. disorders including acute and chronic pain, motor neuron disease and epilepsy. Tap1a-OPT1 showed increased potency for the off-target NaV1.4, while this off-target activity was absent in Tap1a-OPT2. This enhanced potency arose through a slowed off-rate mechanism. Optimized inhibition of NaV channels observed in vitro translated in vivo, with reversal of nocifensive behaviors in a murine model of NaV-mediated pain also enhanced by Tap1a-OPT. Mol. docking studies suggested that improved interactions within loops 3 and 4, and C-terminal of Tap1a-OPT and the NaV channel voltage-sensor domain II were the main drivers of potency optimization. Overall, the rationally designed peptide Tap1a-OPT displayed new and refined structure-function features which are likely the major contributors to its enhanced bioactive properties observed in vivo. This work contributes to the rapid engineering and optimization of potent spider peptides multi-targeting NaV channels, and the research into novel drugs to treat neurol. diseases.

Frontiers in Molecular Biosciences published new progress about Acute pain. 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, SDS of cas: 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Palmquist, Karl H. published the artcileReciprocal cell-ECM dynamics generate supracellular fluidity underlying spontaneous follicle patterning, Quality Control of 21829-25-4, the main research area is supracellular fluidity extracellular matrix follicle cell; active soft matter; biophysics; contractility; emergence; extracellular matrix; mechanics; mechanosensation; morphogenesis; multicellular; organogenesis; periodic patterning; self-organization; skin.

During vertebrate embryogenesis, cell collectives engage in coordinated behavior to form tissue structures of increasing complexity. In the avian skin, assembly into follicles depends on intrinsic mech. forces of the dermis, but how cell mechanics initiate pattern formation is not known. Here, we reconstitute the initiation of follicle patterning ex vivo using only freshly dissociated avian dermal cells and collagen. We find that contractile cells phys. rearrange the extracellular matrix (ECM) and that ECM rearrangement further aligns cells. This exchange transforms a mech. unlinked collective of dermal cells into a continuum, with coherent, long-range order. Combining theory with experiment, we show that this ordered cell-ECM layer behaves as an active contractile fluid that spontaneously forms regular patterns. Our study illustrates a role for mesenchymal dynamics in generating cell-level ordering and tissue-level patterning through a fluid instability-processes that may be at play across morphol. symmetry-breaking contexts.

Cell (Cambridge, MA, United States) published new progress about Aggregates. 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, Quality Control of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Chen, Jinqin published the artcileA novel ω-conotoxin Bu8 inhibiting N-type voltage-gated calcium channels displays potent analgesic activity, HPLC of Formula: 21829-25-4, the main research area is conotoxin voltage gated calcium channel analgesic activity; Analgesic activity; Bu8; DIEA, diisopropylethylamine; ESI-MS, electrospray ionization-mass spectroscopy; Fmoc, N-(9-fluorenyl)methyloxy-carbonyl; HBTU, 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate; HOBt, 1-hydroxybenzotriazole; IC50, half-maximal inhibitory concentration; N-type calcium ion channel; RP-HPLC, reversed phase high-performance liquid chromatography; Structure–activity relationship; TFA, trifluoroacetic acid; ω-conotoxin.

A ω-Conotoxins inhibit N-type voltage-gated calcium (CaV2.2) channels and exhibit efficacy in attenuating neuropathic pain but have a low therapeutic index. Here, we synthesized and characterized a novel ω-conotoxin, Bu8 from Conus bullatus, which consists of 25 amino acid residues and three disulfide bridges. Bu8 selectively and potently inhibits depolarization-activated Ba2+ currents mediated by rat CaV2.2 expressed in HEK293T cells (IC50 = 89 nmol/L). Bu8 is two-fold more potent than ω-conotoxin MVIIA, a ω-conotoxin currently used for the treatment of severe chronic pain. It also displays potent analgesic activity in animal pain models of hot plate and acetic acid writhing but has fewer side effects on mouse motor function and lower toxicity in goldfish. Its lower side effects may be attributed to its faster binding rate and higher recovery ratios. The NMR structure demonstrates that Bu8 contains a small irregular triple β-strand. The structure-activity relationships of Bu8 Ala mutants and Bu8/MVIIA hybrid mutants demonstrate that the binding mode of CaV2.2 with the amino acid residues in loop 1 and loop 2 of Bu8 is different from that of MVIIA. This study characterizes a novel, more potent ω-conotoxin and provides new insights for designing CaV2.2 antagonists.

Acta Pharmaceutica Sinica B published new progress about Analgesics. 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, HPLC of Formula: 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem