[CAS NO. 125404-04-8] TCN238
PRODUCTS SPECIFICATIONS [125404-04-8]
DESCRIPTION [125404-04-8]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 197.24 |
| Molecular Formula | C12H11N3 |
| SMILES | NC1=NC=CC(/C=C/C2=CC=CC=C2)=N1 |
Summary
TCN238 is an orally bioavailable mGlu4 receptor positive allosteric modulator (PAM) with an EC 50 of 1 μM [1] .
IC50 & Target
|
mGlu4 Receptor 1 μM (EC 50 ) |
In Vitro
In the rat mGlu4 PAM in vitro assay the EC 50 of TCN238 (Compound 11) is 1 μM which is comparable to the human assay. TCN238 is screened in rat and human mGlu5 assays, the IC 50 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 [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
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 [1] . 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 [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 150 mg/mL ( 760.49 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 5.0700 mL | 25.3498 mL | 50.6997 mL |
| 5 mM | 1.0140 mL | 5.0700 mL | 10.1399 mL |
| 10 mM | 0.5070 mL | 2.5350 mL | 5.0700 mL |
References
- [1] East SP, et al. An orally bioavailable positive allosteric modulator of the mGlu4 receptor with efficacy in an animal model of motor dysfunction. 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.