TCN 238

Research use only, not for human use.

TCN 238 is an orally bioavailable positive allosteric modulator of the metabotropic glutamate receptor 4 (mGluR4with an EC50 of 1 μM).

TCN 238 is an orally bioavailable positive allosteric modulator of the metabotropic glutamate receptor 4 (mGluR4with an EC50 of 1 μM).

In the rat mGlu4 PAM in vitro assay the EC50 of TCN238 (Compound 11) is 1 μM which is comparable to the human assay. TCN238 is screened in rat and human mGlu5 assays, the IC50 of 11 is >30 μM on human mGlu5and >10 μM on rat mGlu5. TCN238 is run in a receptor screening panel of 68 targets and no activity is observed at ≥50% at 10 μM for any of the receptors. In CaCo-2 cells, TCN238 is found to have good permeability with no apparent efflux issue.

TCN238 is highly CNS penetrant with a concentration of 33.8 μM in the brain. The plasma protein binding in rats is measured as 90% bound. The metabolic stability of TCN238 is assessed in rat and human microsomes and found to be 62% and 83% hepatic blood flow. The limited stability translated into a high in vivo clearance in rats of 75 mL/min/kg and TCN238 has a moderate volume of distribution (2.7 L/kg) with a short mean residence time (0.6 h) when dosed at 2 mg/kg via intravenous injection. TCN238 is orally bioavailable and 30 min following administration of a30 mg/kg dose, the plasma concentration is found to be 11.6 μM. TCN 238 does not affect the performance of the learned task. However, the expression level of GRM4 in the hippocampus is reliable down-regulated five days after treatment with TCN 238. In addition, the expression level of GABRA1, encoding GABAA α-subunit is downregulated five days after the treatment in the frontal cortex.

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Neuroscience

GluR

mGluR

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125404-04-8

197.24

C12H11N3

>98% (HPLC)

DMSO:150 mg/mL (760.49 mM)

Nc1nccc(/C=C/c2ccccc2)n1

(E)-4-(2-Phenylethenyl)-2-pyrimidinamine

(-20℃)

With Ice Pack

≥ 2 years