NPS 2390是代谢性谷氨酸受体1（mGluR1）和5（mGluR5）的非竞争性拮抗剂。
Cas No.:226878-01-9
Sample solution is provided at 25 µL, 10mM.
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NPS 2390 is a non-competitive antagonist of metabolic glutamate receptors 1 (mGluR1) and 5 (mGluR5)[1, 2]. NPS 2390 is a selective calcium-sensing receptor (CaSR) antagonist capable of regulating the phenotypic modulation of hypoxic human pulmonary arterial smooth muscle cells by modulating autophagy[3]. NPS 2390 can ameliorate cardiac injury induced by ischemia/reperfusion[4].
In vitro, treatment of human pulmonary arterial smooth muscle cells (HPASMCs) with NPS 2390 (10µM) for 24h reduced the expression of intracellular autophagy proteins and the synthetic phenotype marker protein osteopontin; it inhibited the downstream PI3K/Akt/mTOR signaling pathway while upregulating the expression of the contractile phenotype markers SMA-α and calponin[3]. Treatment of rat hippocampal cultures with NPS 2390 (10µM) reversed the neuronal injury and apoptosis induced jointly by hypoxia/reoxygenation (H/R) treatment and the calcium-sensing receptor (CaSR) agonist GdCl3; it prevented the GdCl3-induced reduction in neuronal count and decline in cell viability, and significantly lowered the expression levels of caspase-3, Bax, and cytochrome c[5].
In vivo, subcutaneous administration of NPS 2390 (1.5mg/kg) twice to rats with traumatic brain injury (TBI) significantly attenuated cerebral edema, improved neurological function, reduced levels of Caspase-3 and the number of apoptotic neurons in brain tissue, upregulated the expression of the anti-apoptotic protein Bcl-2, downregulated the expression of the pro-apoptotic protein Bax, and reduced the subsequent release of cytochrome c into the cytosol[6]. Treatment of rats with kidney stones via intraperitoneal injection of NPS 2390 (200mg/kg) for four weeks significantly reduced blood urea and serum creatinine levels, lowered the incidence of urinary tract infections, and decreased the expression levels of stone-associated proteins such as ERK, KIM-1, and OPN[7].
References:
[1] Miller B, Moreno N, Gutierrez B A, et al. Microtransplantation of postmortem native synaptic mGluRs receptors into Xenopus oocytes for their functional analysis[J]. Membranes, 2022, 12(10): 931.
[2] Vaidya A, Jain S, K. Jain A, et al. Metabotropic glutamate receptors: a review on prospectives and therapeutic aspects[J]. Mini Reviews in Medicinal Chemistry, 2013, 13(13): 1967-1981.
[3] Peng X, Wei C, Li H Z, et al. NPS2390, a selective calcium-sensing receptor antagonist controls the phenotypic modulation of hypoxic human pulmonary arterial smooth muscle cells by regulating autophagy[J]. Journal of Translational Internal Medicine, 2019, 7(2): 59-68.
[4] Gan R, Hu G, Zhao Y, et al. Post-conditioning protecting rat cardiomyocytes from apoptosis via attenuating calcium-sensing receptor-induced endo (sarco) plasmic reticulum stress[J]. Molecular and cellular biochemistry, 2012, 361(1): 123-134.
[5] Wang P, Wang L, Wang S, et al. Effects of calcium-sensing receptors on apoptosis in rat hippocampus during hypoxia/re-oxygenation through the ERK1/2 pathway[J]. International journal of clinical and experimental medicine, 2015, 8(8): 12858.
[6] Xue Z, Song Z, Wan Y, et al. Calcium-sensing receptor antagonist NPS2390 attenuates neuronal apoptosis though intrinsic pathway following traumatic brain injury in rats[J]. Biochemical and biophysical research communications, 2017, 486(2): 589-594.
[7] Li X, Chen S, Feng D, et al. Calcium-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[J]. Renal failure, 2021, 43(1): 465-476.
NPS 2390是代谢性谷氨酸受体1（mGluR1）和5（mGluR5）的非竞争性拮抗剂[1, 2]。NPS 2390是一种选择性钙感应受体拮抗剂，能够通过调控自噬来控制缺氧人类肺动脉平滑肌细
NPS 2390是代谢性谷氨酸受体1（mGluR1）和5（mGluR5）的非竞争性拮抗剂[1, 2]。NPS 2390是一种选择性钙感应受体（CaSR）拮抗剂，能够通过调控自噬来控制缺氧人类肺动脉平滑肌细胞的表型调节[3]。NPS 2390能够改善缺血/再灌注引起的心脏损伤[4]。
在体外，NPS 2390（10µM）处理人类肺动脉平滑肌细胞（HPASMCs）24h，降低了细胞内自噬蛋白和合成表型标记蛋白骨质素的表达，抑制了下游 PI3K/Akt/mTOR信号通路，提高了收缩表型标记蛋白SMA-ɑ和钙基素的表达[3]。NPS 2390（10µM）处理大鼠海马体培养物，逆转了由缺氧/复氧（H/R）处理和钙敏感受体（CaSR）激动剂GdCl3共同导致的大鼠海马神经元损伤与凋亡，阻止了GdCl3所引起的神经元数量减少和细胞活力下降，显著降低了caspase-3、Bax和细胞色素c的表达水平[5]。
在体内，NPS 2390（1.5mg/kg）通过皮下注射治疗创伤性脑损伤（TBI）大鼠2次，显著减轻了脑水肿，改善了神经功能，降低了脑组织中Caspase-3的水平及凋亡神经元的数量，上调了抗凋亡蛋白Bcl-2的表达，下调了促凋亡蛋白Bax的表达，并减少了随后细胞色素c向细胞溶质的释放[6]。NPS 2390（200mg/kg）通过腹腔注射治疗肾结石大鼠4周，显著降低了血尿素和血清肌酐值，降低了尿路感染率，降低了ERK、KIM-1和OPN等结石相关蛋白表达水平[7]。
| Cell experiment [1]: | |
Cell lines | Human pulmonary artery smooth muscle cells (HPASMCs) |
Preparation Method | HPASMCs were treated with NPS 2390 (10μM) for 24h under hypoxic or normoxic conditions. The expressions of proliferation protein, phenotypic marker protein, and autophagy protein in human PASMCs were determined by western blot. |
Reaction Conditions | 10µM; 24h |
Applications | The addition of NPS 2390 decreased the expression of autophagy protein and synthetic phenotype marker protein osteopontin and increased the expression of contractile phenotype marker protein SMA-ɑ and calponin via suppressing downstream PI3K/Akt/mTOR signal pathways. |
| Animal experiment [2]: | |
Animal models | Sprague Dawley rats |
Preparation Method | Rats were randomly assigned to three groups: the sham group, the TBI+vehicle group, the TBI+NPS2390 group. NPS 2390 (1.5mg/kg) was infused subcutaneously at 30min and 120min after TBI. Subsequently, the rats were euthanized by decapitation, and their brain tissue was rapidly harvested. The modified Neurological Severity Score (mNSS) was employed to assess the effects of NPS 2390 on neurological dysfunction in the animals following TBI. At 24h post-TBI, the neurological function of the rats in each group was evaluated in a blinded manner through motor, sensory, reflex, and balance tests. The parietal cortex surrounding the ipsilateral injury core (on the injured side)—as well as the corresponding region in the sham-operated group—was rapidly dissected and snap-frozen in liquid nitrogen for preservation. |
Dosage form | 1.5mg/kg; s.c. |
Applications | NPS 2390 significantly attenuated cerebral edema following traumatic brain injury (TBI) and improved neurological function. NPS 2390 reduced both Caspase-3 levels and the number of apoptotic neurons; concurrently, NPS 2390 upregulated the expression of the anti-apoptotic protein Bcl-2, downregulated the expression of the pro-apoptotic protein Bax, and reduced the subsequent release of cytochrome c into the cytosol. |
References: | |
| Cas No. | 226878-01-9 | SDF | |
| 化学名 | N-((1r,3R,5r,7S)-adamantan-1-yl)quinoxaline-2-carboxamide | ||
| Canonical SMILES | O=C(C1=NC2=CC=CC=C2N=C1)N[C@]3(C[C@@H]4C5)C[C@H]5C[C@H](C4)C3 | ||
| 分子式 | C19H21N3O | 分子量 | 307.39 |
| 溶解度 | DMSO : 15.62 mg/mL | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.2532 mL | 16.266 mL | 32.532 mL |
| 5 mM | 650.6 μL | 3.2532 mL | 6.5064 mL |
| 10 mM | 325.3 μL | 1.6266 mL | 3.2532 mL |
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