JNJ 16259685是一种强效且选择性的mGlu1受体拮抗剂，IC50值为19nM。
Cas No.:409345-29-5
Sample solution is provided at 25 µL, 10mM.
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JNJ 16259685 is a potent and selective mGlu1 receptor antagonist with an IC50 value of 19nM[1]. JNJ 16259685 acts on the mGlu1 receptor in a non-competitive manner and completely inhibits the increase in intracellular Ca2+ concentration of cells induced by glutamate, with an IC50 value of 3.24nM and excellent brain permeability [2]. JNJ 16259685 has been widely used to block the mGluR1-dependent currents in dopamine neurons[3].
In vitro, JNJ 16259685 treatment (10μM) for 24h can eliminate the increase in intracellular Ca2+ caused by glutamate and prevent glutamate-induced cell apoptosis in rat neuron cells[4].
In vivo, JNJ 16259685 treatment via a single intraperitoneal injection at a dose of 8mg/kg of JNJ 16259685 for 30 minutes inhibited the isolation-induced aggressive behavior in male mice[5]. In rats with subarachnoid hemorrhage (SAH), intraperitoneal injection of JNJ 16259685 (10mg/kg) at 2 hours, 24 hours and 48 hours after the injury can alleviate blood-brain barrier damage and brain edema, restore the level of vascular active polypeptide (VASP) and inhibit the expression of AQP4[6]. A single subcutaneous injection of 1mg/kg dose of JNJ 16259685 for 30min impaired the movement and coordination abilities of mice, and inhibited the exploratory behavior[7].
References:
[1] Fukunaga I, Yeo C H, Batchelor A M. Potent and specific action of the mGlu1 antagonists YM‐298198 and JNJ16259685 on synaptic transmission in rat cerebellar slices[J]. British journal of pharmacology, 2007, 151(6): 870-876.
[2] Steckler T, Lavreysen H, Oliveira A M, et al. Effects of mGlu1 receptor blockade on anxiety-related behaviour in the rat lick suppression test[J]. Psychopharmacology, 2005, 179(1): 198-206.
[3] Kramer P F, Williams J T. Cocaine decreases metabotropic glutamate receptor mGluR1 currents in dopamine neurons by activating mGluR5[J]. Neuropsychopharmacology, 2015, 40(10): 2418-2424.
[4] Zhang Z, Liu J, Fan C, et al. The GluN1/GluN2B NMDA receptor and metabotropic glutamate receptor 1 negative allosteric modulator has enhanced neuroprotection in a rat subarachnoid hemorrhage model[J]. Experimental neurology, 2018, 301: 13-25.
[5] Navarro J F, De Castro V, Martín-López M. JNJ16259685, a selective mGlu1 antagonist, suppresses isolation-induced aggression in male mice[J]. European Journal of Pharmacology, 2008, 586(1-3): 217-220.
[6] Zhang C, Jiang M, Wang W, et al. Selective mGluR1 negative allosteric modulator reduces blood–brain barrier permeability and cerebral edema after experimental subarachnoid hemorrhage[J]. Translational stroke research, 2020, 11(4): 799-811.
[7] Hodgson R A, Hyde L A, Guthrie D H, et al. Characterization of the selective mGluR1 antagonist, JNJ16259685, in rodent models of movement and coordination[J]. Pharmacology Biochemistry and Behavior, 2011, 98(2): 181-187.
JNJ 16259685是一种强效且选择性的mGlu1受体拮抗剂，IC50值为19nM[1]。JNJ 16259685以非竞争性方式作用于mGlu1受体，能完全抑制谷氨酸诱导的细胞内Ca2+浓度的升高，IC50值为3.24nM，并具有优异的脑通透性[2]。JNJ 16259685已被广泛用于阻断多巴胺神经元中mGluR1依赖性电流[3]。
在体外，使用10μM的JNJ 16259685 处理大鼠神经元细胞24小时，可消除谷氨酸引起的细胞内Ca2+增加，并防止谷氨酸诱导的细胞凋亡[4]。
在体内，单次腹腔注射8mg/kg剂量的 JNJ 16259685，持续 30 分钟，可抑制雄性小鼠由隔离诱发的攻击行为[5]。在蛛网膜下腔出血（SAH）大鼠中，于损伤后2小时、24小时和48小时腹腔注射JNJ 16259685（10mg/kg），可减轻血脑屏障损伤和脑水肿，恢复vascular active polypeptide (VASP)水平，并抑制AQP4的表达[6]。单次皮下注射1mg/kg剂量的JNJ 16259685，持续30分钟，会损害小鼠的运动和协调能力，并抑制小鼠探索行为[7]。
| Cell experiment [1]: | |
Cell lines | Cortical neuron cells |
Preparation Method | Cortical neuron cells plated in neurobasal medium supplemented with 2% B27, 1% l-glutamine and 0.3% d-glucose, 1% fetal bovine serum (FBS) in 60mm dishes at 106 cells/dish in a humidified atmosphere containing 5% CO2 at 37°C. The cells were switched to the stimulation medium (culture medium loaded with 100μM glutamate or 100μM glutamate plus 10μM JNJ 16259685) for 24h. Then, analyze the apoptosis rate. |
Reaction Conditions | 10μM; 24h |
Applications | JNJ 16259685 treatment significantly reduced glutamate-induced cell apoptosis in neuron cells. |
| Animal experiment [2]: | |
Animal models | Male C57BL/6J mice |
Preparation Method | Male C57BL/6J mice (25-30g) were kept in temperature-controlled (21°C-25°C) and humidity-maintained (40%-70%) rooms with a 12-h light/dark cycle. Water and food were provided freely. JNJ 16259685 was suspended in 10% hydroxypropyl-betacyclodextrin (HPβCD) and injected subcutaneously (s.c.) 30min prior to rotarod testing in mice. |
Dosage form | 1mg/kg for once; s.c. |
Applications | JNJ 16259685 treatment impaired performance of mice on the rotarod. |
References: | |
| Cas No. | 409345-29-5 | SDF | |
| 化学名 | (3,4-dihydro-2H-pyrano[2,3-b]quinolin-7-yl)((1s,4s)-4-methoxycyclohexyl)methanone | ||
| Canonical SMILES | O=C(C1=CC=C2N=C3OCCCC3=CC2=C1)[C@@H](CC4)CC[C@@H]4OC | ||
| 分子式 | C20H23NO3 | 分子量 | 325.41 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.073 mL | 15.3652 mL | 30.7305 mL |
| 5 mM | 614.6 μL | 3.073 mL | 6.1461 mL |
| 10 mM | 307.3 μL | 1.5365 mL | 3.073 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
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2.
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- Purity: >98.00% Appearance: A solid
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