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JNJ-42153605

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Chemical Structure| 1254977-87-1 同义名 : -
CAS号 : 1254977-87-1
货号 : A725030
分子式 : C22H23F3N4
纯度 : 99%+
分子量 : 400.44
MDL号 : MFCD22199231
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 16 mg/mL(39.96 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 Metabotropic glutamate receptors (mGlu) are a family of class C G-protein-coupled receptors responsible for the fine-tuning of synaptic efficacy. The mGlu2 receptor is a member of the group II subfamily that negatively regulates the release of glutamate and GABA. JNJ-42153605 is a potent and selective mGlu2 positive allosteric modulator with an EC50 value of 17nM and Emax of 285%. The IC50 value of JNJ-42153605 for mGlu2 PAM binding is 15nM. The lipophilic ligand efficiency and lipophilicity-corrected ligand efficiency values of JNJ-42153605 are 5.2 and 9.8, respectively. The oral administration of JNJ-42153605 (3mg/kg) suppressed rapid eye movement (REM) sleep in mice during the first 2 h after treatment when compared to vehicle controls. JNJ-42153605 also prolonged the onset latency of REM sleep onset in mice. In the mouse model of phencyclidine-induced hyperlocomotion, JNJ-42153605 significantly attenuated phencyclidine-induced locomotor activity in a dose-dependent manner with an ED50 of 5.4mg/kg[4]. In the 6 Hz (32 mA stimulus intensity) model, median effective dose (ED50) values for JNJ‐42153605 were 3.8 mg/kg[5].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.50mL

0.50mL

0.25mL

12.49mL

2.50mL

1.25mL

24.97mL

4.99mL

2.50mL
参考文献

[1]Leurquin-Sterk G, Celen S, et al. What We Observe In Vivo Is Not Always What We See In Vitro: Development and Validation of 11C-JNJ-42491293, A Novel Radioligand for mGluR2. J Nucl Med. 2017 Jan;58(1):110-116.

[2]Cid JM, Tresadern G, et al. Discovery of 3-cyclopropylmethyl-7-(4-phenylpiperidin-1-yl)-8-trifluoromethyl[1,2,4]triazolo[4,3-a]pyridine (JNJ-42153605): a positive allosteric modulator of the metabotropic glutamate 2 receptor. J Med Chem. 2012 Oct 25;55(20):8770-89.

[3]Ahnaou A, Lavreysen H, et al. mGlu2 Receptor Agonism, but Not Positive Allosteric Modulation, Elicits Rapid Tolerance towards Their Primary Efficacy on Sleep Measures in Rats. PLoS One. 2015 Dec 11;10(12):e0144017.

[4]Cid JM, Tresadern G, Vega JA, de Lucas AI, Matesanz E, Iturrino L, Linares ML, Garcia A, Andrés JI, Macdonald GJ, Oehlrich D, Lavreysen H, Megens A, Ahnaou A, Drinkenburg W, Mackie C, Pype S, Gallacher D, Trabanco AA. Discovery of 3-cyclopropylmethyl-7-(4-phenylpiperidin-1-yl)-8-trifluoromethyl[1,2,4]triazolo[4,3-a]pyridine (JNJ-42153605): a positive allosteric modulator of the metabotropic glutamate 2 receptor. J Med Chem. 2012 Oct 25;55(20):8770-89.

[5]Metcalf CS, Klein BD, Smith MD, Pruess T, Ceusters M, Lavreysen H, Pype S, Van Osselaer N, Twyman R, White HS. Efficacy of mGlu2 -positive allosteric modulators alone and in combination with levetiracetam in the mouse 6 Hz model of psychomotor seizures. Epilepsia. 2017 Mar;58(3):484-493.