Category: 21829-25-4

Peng, Chiung-Chi published the artcileNifedipine upregulates ATF6-α, caspases -12, -3, and-7 implicating lipotoxicity-associated renal ER stress, HPLC of Formula: 21829-25-4, the main research area is endoplasmic reticular stress nifedipine ATF6 lipotoxicity; ATF6α, lipotoxicity; ER stress; chronic kidney disease; nifedipine.

Nifedipine (NF) is reported to have many beneficial effects in antihypertensive therapy. Recently, we found that NF induced lipid accumulation in renal tubular cells. Palmitic acid-induced renal lipotoxicity was found to be partially mediated by endoplasmic reticular (ER) stress, while it can also be elicited by NF in kidney cells; we examined the induction of suspected pathways in both in vitro and in vivo models. NRK52E cells cultured in high-glucose medium were treated with NF (30μM) for 24-48 h. ER stress-induced lipotoxicity was explored by staining with thioflavin T and Nile red, transmission electron microscopy, terminal uridine nick-end labeling, and Western blotting. ER stress was also investigated in rats with induced chronic kidney disease (CKD) fed NF for four weeks. NF induced the production of unfolded protein aggregates, resulting in ER stress, as evidenced by the upregulation of glucose-regulated protein, 78 kDa (GRP78), activating transcription factor 6α (ATF6α), C/EBP-homologous protein (CHOP), and caspases-12, -3, and -7. In vitro early apoptosis was more predominant than late apoptosis. Most importantly, ATF6α was confirmed to play a unique role in NF-induced ER stress in both models. CKD patients with hypertension should not undergo NF therapy. In cases where it is required, alleviation of ER stress should be considered to avoid further damaging the kidneys.

International Journal of Molecular Sciences published new progress about Apoptosis. 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

Shen, Xiao published the artcileSevere adverse cutaneous reactions induced by gefitinib combined with antihypertensive and antihyperlipidemic drugs in lung cancer: a case report, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is severe adverse cutaneous reaction induced gefitinib antihypertensive antihyperlipidemic lungcancer.

The incidence of lung cancer is increasing yearly worldwide, and targeted medicines are the main choice for lung cancer patients. However, there has been no relevant research about the anal. and adjustment of drug combinations for cancer patients with hypertension and hyperlipidemia until now. Here, we reported a case of medicine adjustment for a patient of lung cancer with hypertension and hyperlipidemia. The patient was diagnosed as right lung adenocarcinoma with lymph node metastasis and continued taking gefitinib tablets to maintain therapeutic efficacy after the end of chemotherapy. Severe paronychia and a high plasma concentration of gefitinib were noticed when the patient visited the hospital for reexamination The clin. pharmacist found that the patient took nifedipine sustained-release tablets and simvastatin tablets simultaneously, and these medicines were all substrates of CYP3A4. The clin. pharmacist suggested replacing the medicines for hypertension and hyperlipidemia with valsartan capsules (Diovan) and rosuvastatin calcium tablets (Crestor), resp. The adverse cutaneous reactions were greatly relieved, and the plasma concentration of gefitinib was decreased when another reexamination was performed. Therapeutic drug monitoring was an important method in our case and provided valuable information to develop individualized treatment strategies. For cancer patients suffering from other diseases such as hypertension and hyperlipidemia, it is necessary to pay special attention to the drug-drug interactions and metabolic pathways among drug combinations.

Anti-Cancer Drugs published new progress about Antihypertensives. 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, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Maafi, Mounir published the artcilePhotokinetics of Dacarbazine and Nifedipine under polychromatic light irradiation and their application as new reliable actinometers for the ultraviolet range, Related Products of pyridine-derivatives, the publication is Scientific Reports (2022), 12(1), 7622, database is CAplus and MEDLINE.

The photokinetic behavior of drugs driven by polychromatic light is an area of pharmaceutics that has not received a lot of attention. Most often, such photokinetic data is treated by thermal kinetic models (i.e., the classical 0th-, 1st- or 2nd-order equations). Such models were not anal. derived from the rate-laws of the photodegradation reactions. Polychromatic light kinetic modeling is hence of importance, as a means to providing adequate toolkits and metrics. This paper aims at proposing two reliable drug-actinometers useful for polychromatic UVA range. The general actinometric methodol. offered here is also useful for any drugs/materials obeying a primary photoprocess where both reactant and photoproduct absorb the incident light, of the AB(1φ)εB≠0 type. The present method has been consolidated by the η-order kinetics. This framework further demonstrated the lamp-specificity of actinometers. Overall, Dacarbazine and Nifedipine photodegradations obeyed η-order kinetics, and stand as effective actinometers that can be recommended for the ICH Q1b photostability testing.

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 C17H18N2O6, Related Products of pyridine-derivatives.

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

Hashemi, Marzieh published the artcileEnhancing the Anticonvulsant Effects of Nifedipine in Rats Through Encapsulation with Water-Soluble β-Cyclodextrin Polymer, Related Products of pyridine-derivatives, the publication is Pharmaceutical Chemistry Journal (2022), 55(10), 1023-1027, database is CAplus.

Encapsulation is one of the efficient methods recently developed for improving drug delivery. The present study was designed to encapsulate nifedipine (NIF) by water-soluble β-cyclodextrin polymer (β-CDP) and to evaluate the effects of this carrier on NIF-induced anticonvulsant effects. Adult male Wistar rats weighting 200 – 250 g (n = 7) received NIF or encapsulated NIF (β-CDP/NIF) (5, 10 and 20 mg/kg, i.p.), diazepam (2 mg/kg, i.p. as pos. control), and vehicle. Then, pentylenetetrazol (PTZ, 80 mg/kg, i.p.) was injected about 30 min after the drug injection. Changes in the onset time of seizures and duration of their different stages (tonic and tonic-clonic) and total convulsions duration, percentage mortality and percentage of seizure protection were assessed in all test groups. Latency of the seizure onset and duration of tonic and tonic-clonic seizures were significantly decreased in β-CDP/NIF group in comparison with NIF-treated rats (p < 0.05). On the other hand, percentage mortality was significantly decreased and percentage protection was increased by β-CDP/NIF in comparison to NIF (p < 0.05). Therefore, it was concluded that the encapsulation of NIF by β-CDP led to enhancement of the anticonvulsant effects of NIF in rats.

Pharmaceutical Chemistry 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 C17H18N2O6, Related Products of pyridine-derivatives.

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

Principe, Daniel R. published the artcileCalcium channel blockers potentiate gemcitabine chemotherapy in pancreatic cancer, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the publication is Proceedings of the National Academy of Sciences of the United States of America (2022), 119(18), e2200143119, database is CAplus and MEDLINE.

There is currently no effective treatment for pancreatic ductal adenocarcinoma (PDAC). While palliative chemotherapy offers a survival benefit to most patients, nearly all will eventually progress on treatment and long-term survivability remains poor. Given the lack of subsequent line treatment options, in this study, we sought to identify novel strategies to prevent, delay, or overcome resistance to gemcitabine, one of the most widely used medications in PDAC. Using a combination of single-cell RNA sequencing and high-throughput proteomic anal., we identified a subset of gemcitabine-resistant tumor cells enriched for calcium/calmodulin signaling. Pharmacol. inhibition of calcium-dependent calmodulin activation led to the rapid loss of drug-resistant phenotypes in vitro, which addnl. single-cell RNA sequencing identified was due to impaired activation of the RAS/ERK signaling pathway. Consistent with these observations, calcium chelation or depletion of calcium in the culture media also impaired ERK activation in gemcitabine-resistant cells, and restored therapeutic responses to gemcitabine in vitro. We observed similar results using calcium channel blockers (CCBs) such as amlodipine, which inhibited prosurvival ERK signaling in vitro and markedly enhanced therapeutic responses to gemcitabine in both orthotopic xenografts and transgenic models of PDAC. Combined, these results offer insight into a potential means of gemcitabine resistance and suggest that select CCBs may provide a clin. benefit to PDAC patients receiving gemcitabine-based chemotherapy.

Proceedings of the National Academy of Sciences of the United States of America 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

Brecklinghaus, Tim published the artcileThe hepatocyte export carrier inhibition assay improves the separation of hepatotoxic from non-hepatotoxic compounds, COA of Formula: C17H18N2O6, the publication is Chemico-Biological Interactions (2022), 109728, database is CAplus and MEDLINE.

An in vitro/in silico method that determines the risk of human drug induced liver injury in relation to oral doses and blood concentrations of drugs was recently introduced. This method utilizes information on the maximal blood concentration (Cmax) for a specific dose of a test compound, which can be estimated using physiol.-based pharmacokinetic modeling, and a cytotoxicity test in cultured human hepatocytes. In the present study, we analyzed if the addition of an assay that measures the inhibition of bile acid export carriers, like BSEP and/or MRP2, to the existing method improves the differentiation of hepatotoxic and non-hepatotoxic compounds Therefore, an export assay for 5-chloromethylfluorescein diacetate (CMFDA) was established. We tested 36 compounds in a concentration-dependent manner for which the risk of hepatotoxicity for specific oral doses and the capacity to inhibit hepatocyte export carriers are known. Compared to the CTB cytotoxicity test, substantially lower EC10 values were obtained using the CMFDA assay for several known BSEP and/or MRP2 inhibitors. To quantify if the addition of the CMFDA assay to our test system improves the overall separation of hepatotoxic from non-hepatotoxic compounds, the toxicity separation index (TSI) was calculated We obtained a better TSI using the lower alert concentration from either the CMFDA or the CTB test (TSI: 0.886) compared to considering the CTB test alone (TSI: 0.775). In conclusion, the data show that integration of the CMFDA assay with an in vitro test battery improves the differentiation of hepatotoxic and non-hepatotoxic compounds in a set of compounds that includes bile acid export carrier inhibitors.

Chemico-Biological Interactions 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, COA of Formula: C17H18N2O6.

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

Held, Katharina published the artcilePharmacological properties of TRPM3 isoforms are determined by the length of the pore loop, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the publication is British Journal of Pharmacology (2022), 179(14), 3560-3575, database is CAplus and MEDLINE.

Background and Purpose : Transient receptor potential melastatin 3 (TRPM3) is a non-selective cation channel that plays a pivotal role in the peripheral nervous system as a transducer of painful heat signals. Alternative splicing gives rise to several TRPM3 variants. The functional consequences of these splice isoforms are poorly understood. Here, the pharmacol. properties of TRPM3 variants arising from alternative splicing in the pore-forming region were compared. Exptl. Approach : Calcium microfluorimetry and patch clamp recordings were used to compare the properties of heterologously expressed TRPM3α1 (long pore variant) and TRPM3α2-α6 (short pore variants). Furthermore, site-directed mutagenesis was done to investigate the influence of the length of the pore loop on the channel function. Key Results : All short pore loop TRPM3α variants (TRPM3α2-α6) were activated by the neurosteroid pregnenolone sulfate (PS) and by nifedipine, whereas the long pore loop variant TRPM3α1 was insensitive to either compound In contrast, TRPM3α1 was robustly activated by clotrimazole, a compound that does not directly activate the short pore variants but potentiates their responses to PS. Clotrimazole-activated TRPM3α1 currents were largely insensitive to established TRPM3α2 antagonists and were only partially inhibited upon activation of the μ opioid receptor. Finally, by creating a set of mutant channels with pore loops of intermediate length, we showed that the length of the pore loop dictates differential channel activation by PS and clotrimazole. Conclusion and Implications : Alternative splicing in the pore-forming region of TRPM3 defines the channel’s pharmacol. properties, which depend critically on the length of the pore-forming loop.

British Journal of 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, 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