Tag: M.W=300-350

Lavreysen, Hilde published the artcile[³H]R214127: A novel high-affinity radioligand for the mGlu1 receptor reveals a common binding site shared by multiple allosteric antagonists, SDS of cas: 226878-01-9, the publication is Molecular Pharmacology (2003), 63(5), 1082-1093, database is CAplus and MEDLINE.

R214127 was shown to be a potent and noncompetitive metabotropic glutamate 1 (mGlu1) receptor-selective antagonist. The kinetics and pharmacol. of [³H]1-(3,4-dihydro-2H-pyrano[2,3-b]quinolin-7-yl)-2-phenyl-1- ethanone (R214127) binding to rat mGlu1a receptor Chinese hamster ovary (CHO)-dhfr^– membranes was investigated, as well as the distribution of [³H]R214127 binding in rat brain tissue and sections. Specific binding to rat mGlu1a receptor CHO-dhfr^– membranes was ∼92% of total and was optimal at 4°. Full association was reached within 5 min, and [³H]R214127 bound to a single binding site with an apparent K_D of 0.90 nM and a B_max of 6512 fmol/mg of protein. Inhibition experiments showed that [³H]R214127 binding was completely blocked by 2-quinoxaline-carboxamide-N-adamantan-1-yl (NPS 2390), (3aS,6aS)-6a-naphtalan-2-ylmethyl-5-methyliden-hexahydro-cyclopenta[c] furan-1-on (BAY 36-7620), and 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate Et ester (CPCCOEt), but was not displaced by competitive mGlu1 receptor ligands such as glutamate and quisqualate, suggesting that R214127, NPS 2390, BAY 36-7620, and CPCCOEt bind to the same site or mutually exclusive sites. Experiments using rat cortex, striatum, hippocampus and cerebellum revealed that [³H]R214127 labeled a single high-affinity binding site (K_D ∼ 1 nM). B_max values were highest in the cerebellum (4302 fmol/mg of protein) and were 741, 688, and 471 fmol/mg of protein in the striatum, hippocampus, and cortex, resp. The distribution of [³H]R214127 binding in rat brain was investigated in more detail by radioligand autoradiog. A high d. of binding sites was detected in the mol. layer of the cerebellum. Moderate labeling was seen in the CA3 and dentate gyrus of the hippocampus, thalamus, olfactory tubercle, amygdala, and substantia nigra reticulata. The cerebral cortex, caudate putamen, ventral pallidum, and nucleus accumbens showed lower labeling. The high affinity and selectivity of [³H]R214127 for mGlu1 receptors renders this compound the ligand of choice to study the native mGlu1 receptor in brain.

Molecular Pharmacology published new progress about 226878-01-9. 226878-01-9 belongs to quinoxaline, auxiliary class Neuronal Signaling,mGluR, name is N-(Adamantan-1-yl)quinoxaline-2-carboxamide, and the molecular formula is C19H21N3O, SDS of cas: 226878-01-9.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Vanejevs, Maksims published the artcilePositive and Negative Modulation of Group I Metabotropic Glutamate Receptors, Application In Synthesis of 226878-01-9, the publication is Journal of Medicinal Chemistry (2008), 51(3), 634-647, database is CAplus and MEDLINE.

A discriminating pharmacophore model for noncompetitive metabotropic glutamate receptor antagonists of subtype 1 (mGluR1) was developed that facilitated the discovery of moderately active mGluR1 antagonists. One scaffold was selected for the design of several focused libraries where different substitution patterns were introduced. This approach facilitated the discovery of potent mGluR1 antagonists, as well as pos. and neg. mGluR5 modulators, because both receptor subtypes share similar binding pockets. For mGluR1 antagonists, a homol. model of the mGlu1 receptor was established, and a putative binding mode within the receptor’s transmembrane domain was visualized.

Journal of Medicinal Chemistry published new progress about 226878-01-9. 226878-01-9 belongs to quinoxaline, auxiliary class Neuronal Signaling,mGluR, name is N-(Adamantan-1-yl)quinoxaline-2-carboxamide, and the molecular formula is C9H5ClO4S, Application In Synthesis of 226878-01-9.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Liu, Chong published the artcileCaSR activates PKCδ to induce cardiomyocyte apoptosis via ER stress associated apoptotic pathways during ischemia/reperfusion, Application In Synthesis of 226878-01-9, the publication is International Journal of Molecular Medicine (2019), 44(3), 1117-1126, database is CAplus and MEDLINE.

Endoplasmic reticulum (ER) stress can be activated by ischemia/reperfusion (I/R) injury in cardiomyocytes. Persistent ER stress, with an increase in intracellular Ca²⁺ ([Ca²⁺]i) concentration, leads to apoptosis. Protein kinase C (PKC) has a key role in myocardial damage by elevation of [Ca²⁺]i. The calcium-sensing receptor (CaSR), a G protein-coupled receptor, can increase the release of [Ca²⁺]i from the ER through the inositol triphosphate receptor (IP₃R). Intracellular calcium overload has been demonstrated to cause cardiac myocyte apoptosis during I/R. However, the associations between PKC, CaSR and ER stress are not clear. The present study examined the hypothesis that activation of PKCδ by CaSR participates in ER stress-associated apoptotic pathways within myocardial I/R. Rat hearts were subjected to 30 min of ischemia in vivo, followed by reperfusion for 120 min. GdCl₃ (a CaSR activator) was used to elevate the intracellular Ca²⁺ concentration, but the Ca²⁺ concentration in the ER was significantly decreased during I/R. Following exposure to GdCl₃, expression levels of CaSR, glucose-regulated protein 78 (GRP78), Caspase-12, phosphorylated JNK and Caspase-3 were increased, and the ratios of apoptotic myocardial cells were significantly increased. By contrast, following exposure to rottlerin, a PKCδ inhibitor, the expression levels of these proteins and the ratio of apoptotic myocardial cells were significantly reduced. The present study also demonstrated that PKCd translocated into the ER to induce an ER stress response and participate in the ER stress-related apoptosis pathway. These results confirmed that CaSR activated PKCδ to induce cardiomyocyte apoptosis through ER stress-associated apoptotic pathways during I/R in vivo.

International Journal of Molecular Medicine published new progress about 226878-01-9. 226878-01-9 belongs to quinoxaline, auxiliary class Neuronal Signaling,mGluR, name is N-(Adamantan-1-yl)quinoxaline-2-carboxamide, and the molecular formula is C19H21N3O, Application In Synthesis of 226878-01-9.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Li, Shaoxing published the artcileA novel function of calcium sensing receptor in chronic hypoxia-induced pulmonary venous smooth muscle cells proliferation, Recommanded Product: N-(Adamantan-1-yl)quinoxaline-2-carboxamide, the publication is Hypertension Research (2020), 43(4), 271-280, database is CAplus and MEDLINE.

The present study aimed to explore the mechanisms by which CH affects PVSMCs proliferation. PVSMCs were isolated from rat distal pulmonary veins and exposed to CH (4% O₂ for 60 h). The expression of calcium sensing receptor (CaSR) was determined by immunofluorescence, real-time quant. PCR and Western blotting. Cell proliferation was assessed by cell counting, CCK-8 assay, and BrdU incorporation. Apoptosis anal. was examined by flow cytometry. In rat distal PVSMCs, CH increased the cell number and cell viability and enhanced DNA synthesis, which is accompanied by upregulated mRNA and protein expression levels of CaSR. Two neg. CaSR modulators (NPS2143, NPS2390) not only attenuated CH-induced CaSR upregulation but also inhibited CH-induced increases in cell number, cell viability and the proliferation index of PVSMCs, whereas two pos. modulators (spermine, R568) not only amplified CH-induced CaSR upregulation but also intensified CH-induced increases in cell number, cell viability and the proliferation index of PVSMCs. Silencing CaSR with siRNA similarly attenuated the CH-induced enhancement of cell number, cell viability and DNA synthesis in PVSMCs. Neither CH nor downregulation of CaSR with siRNA had an effect on apoptosis in PVSMCs. These results suggest that CaSR mediating excessive proliferation is a new pathogenic mechanism involved in the initiation and progression of distal PVSMCs proliferation under CH conditions.

Hypertension Research published new progress about 226878-01-9. 226878-01-9 belongs to quinoxaline, auxiliary class Neuronal Signaling,mGluR, name is N-(Adamantan-1-yl)quinoxaline-2-carboxamide, and the molecular formula is C19H21N3O, Recommanded Product: N-(Adamantan-1-yl)quinoxaline-2-carboxamide.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Li, Xiaoran published the artcileCalcium-sensing receptor promotes calcium oxalate crystal adhesion and renal injury in Wistar rats by promoting ROS production and subsequent regulation of PS ectropion, OPN, KIM-1, and ERK expression, Quality Control of 226878-01-9, the publication is Renal Failure (2021), 43(1), 465-476, database is CAplus and MEDLINE.

To explore the mechanism of calcium-sensing receptors (CaSRs) during the development of nephrolithiasis. Wistar rats were treated with ethylene glycol to induce calcium oxalate crystallization, and gadolinium chloride (GdCl₃, an agonist of CaSR) and NPS 2390 (an antagonist of CaSR) were added. Oxidative stress (OS) and calcium oxalate crystals in the kidney were observed CaSR expression and the expression of extracellular signal-regulated protein kinase (ERK), OPN, and KIM-1 were determined by western blotting. In addition, renal tubular epithelial cells were isolated from the kidney to observe phosphatidylserine (PS) ectropion using flow cytometric anal. Various biochem. parameters were assessed in serum and urine at the end of the experiment Calcium oxalate increased OS, crystal adhesion, PS ectropion, and the expression of CaSR and ERK, OPN, and KIM-1 in vivo. In addition, lower levels of urine citrate as well as increased serum creatinine and urea levels were observed after treatment with calcium oxalate (p < .05). Compared with calcium oxalate treatment alone, the above deleterious changes were further significantly confirmed by GdCl₃ but were reversed by NPS-2390. However, urine calcium excretion was decreased after ethylene glycol treatment but was significantly reduced by NPS 2390 and increased by GdCl₃ (p < .05). The results suggest that CaSR might play significant roles in the induction of nephrolithiasis in rats by regulating reactive oxygen species (ROS) and PS ectropion and the composition of urine, OPN, KIM-1, and ERK expression.

Renal Failure published new progress about 226878-01-9. 226878-01-9 belongs to quinoxaline, auxiliary class Neuronal Signaling,mGluR, name is N-(Adamantan-1-yl)quinoxaline-2-carboxamide, and the molecular formula is C19H21N3O, Quality Control of 226878-01-9.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider