TCN238 - mGluR Modulator - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETCN238Cat. No.: HY-14419CAS No.: 125404-04-8分式: CHN分量: 197.24作靶點(diǎn): mGluR作通路: GPCR/G Protein; Neuronal Signaling儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 150 mg/mL (760.49 mM)* means so

2、luble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 5.0700 mL 25.3498 mL 50.6997 mL5 mM 1.0140 mL 5.0700 mL 10.1399 mL10 mM 0.5070 mL 2.5350 mL 5.0700 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 TCN238是mGlu4的正變構(gòu)調(diào)節(jié)物，EC50值為1 M。IC50 & Target EC50: 1

3、 M (human or rat mGlu4) 1體外研究In the rat mGlu4 PAM in vitro assay the EC50 of TCN238 is 1 M which is comparable to the human assay.TCN238 is screened in rat and human mGlu5 assays, the IC50 of 11 is 30 M on human mGlu5and 10 M1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEon rat mGlu5. TCN238 is ru

4、n in a receptor screening panel of 68 targets and no activity is observed at 50%at 10 M for any of the receptors. In CaCo-2 cells, TCN238 is found to have good permeability with noapparent efflux issue 1.體內(nèi)研究 TCN238 is highly CNS penetrant with a concentration of 33.8 M in the brain. The plasma prot

5、ein binding inrats is measured as 90% bound. The metabolic stability of TCN238 is assessed in rat and humanmicrosomes and found to be 62% and 83% hepatic blood flow. The limited stability translated into a high invivo clearance in rats of 75 mL/min/kg and TCN238 has a moderate volume of distribution

6、 (2.7 L/kg) with ashort mean residence time (0.6 h) when dosed at 2 mg/kg via intravenous injection. TCN238 is orallybioavailable and 30 min following administration of a30 mg/kg dose, the plasma concentration is found to be11.6 M 1. TCN 238 does not affect the performance of the learned task. Howev

7、er, the expression level ofGRM4 in the hippocampus is reliable down-regulated five days after treatment with TCN 238. In addition, theexpression level of GABRA1, encoding GABAA -subunit is downregulated five days after the treatment inthe frontal cortex 2.PROTOCOLAnimal Rats: TCN 238 is administered

8、 subcutaneously at a dose of 2 mg/kg (volume of 0.5 mL) four times in twoAdministration 2 days (morning and evening). Retrieval of the task is tested 30min after the first and third injections of TCN238, and 5 days after the last injection of the substance. During the retrieval test the animals are

9、placed tothe start box, the door is opened, and the latent period of response is registered. 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. East SP, et al. An orally bioavailable positive allosteric modulator of the mGlu4 receptor with e

10、fficacy in an animal model of motordysfunction. Bioorg Med Chem Lett. 2010 Aug 15;20(16):4901-5.2. Pershina EV, et al. Subacute activation of mGlu4 receptors causes the feedback inhibition of its gene expression in rat brain. Life Sci.2016 May 15;153:50-4.McePdfHeightCaution: Product has not been fully valida