61350-00-3
61350-00-3 structure
- Name: VU 0364770
- Chemical Name: N-(3-chlorophenyl)pyridine-2-carboxamide
- CAS Number: 61350-00-3
- Molecular Formula: C12H9ClN2O
- Molecular Weight: 232.66600
- Catalog: Biochemical Inhibitor Neuronal Signaling GluR antagonist
- Create Date: 2017-05-24 03:47:58
- Modify Date: 2026-07-01 10:00:54
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VU0364770 is an allosteric of metabotropic glutamate receptor 4 (mGlu4) modulator, which exhibits a EC50 of 1.1±0.2 μM at human mGlu4.
| Name | N-(3-chlorophenyl)pyridine-2-carboxamide |
|---|---|
| Synonyms |
2-PyridinecboxaMide, N-(3-chlorophenyl)
SKL856 VU0364770 N-(3-Chlorophenyl)picolinamide VU0364770, 10 mM in DMSO N-(3-chlorophenyl)pyridine-2-cboxamide VU 0364770 //BP VU0364770;VU-0364770 |
| Description | VU0364770 is an allosteric of metabotropic glutamate receptor 4 (mGlu4) modulator, which exhibits a EC50 of 1.1±0.2 μM at human mGlu4. |
|---|---|
| Related Catalog | |
| Target |
EC50: 1.1±0.2 μM (mGlu4)[1] |
| In Vitro | VU0364770 is a selective positive allosteric modulator of mGlu4 in recombinant systems. VU0364770 is a potent PAM of multiple signaling pathways that enhances the response of the rat and human mGlu4 receptors to the endogenous agonist glutamate. VU0364770 produces a concentration-dependent potentiation of the response to an EC20 concentration of glutamate with EC50 of 1.1±0.2 μM and increases the maximal response to glutamate from 100 to 227±17%. Because of concerns that this chemical scaffold might possess activity at MAO, full IC50 determinations is performed for VU0364770 at the MAO-A and MAO-B isoforms; these studies result in Kis of 8.5 and 0.72 μM for human MAO-A and human MAO-B, respectively. When tested at a 10 μM concentration at each mGlu receptor, VU0364770 exhibits weak PAM activity (4.3-fold left shift of the glutamate CRC) at mGlu6 and antagonist activity (3.3-fold right shift of the glutamate CRC) at mGlu5 (compare to the 16.5-fold left shift of the glutamate concentration-response for mGlu4 at 10 μM). When further evaluated in a full concentration-response curve format, VU0364770 exhibits antagonist activity at mGlu5 with a potency of 17.9±5.5 μM and PAM activity at mGlu6 with a potency of 6.8±1.7 μM (compare with the potency of VU0364770 on the rat mGlu4 receptor of 290±80 nM)[1]. |
| In Vivo | VU0364770 exhibits suitable pharmacokinetic properties for systemic dosing in animal models. After intravenous administration, VU0364770 is rapidly clears from the systemic circulation (165 ml/min/kg) and exhibits a volume of distribution of 2.92 L/kg. VU0364770 is a highly protein-bound ligand displaying free fractions of 2.7 and 1.8% in human and rat plasma, respectively. VU0364770 also shows an improved pharmacokinetic profile relative to previously reported mGlu4 PAMs with enhanced central penetration and a total brain-to-plasma ratio of more than 1 after systemic administration of a 10 mg/kg dose. VU0364770 produces a dose-dependent reversal of haloperidol-induced catalepsy. VU0364770 dose-dependently reverses haloperidol (0.75 mg/kg)-induced catalepsy in rats, significant at doses of 10 to 56.6 mg/kg, after subcutaneous dosing (F6,69=8.04; p<0.001)[1]. |
| Kinase Assay | The effects of VU0364770 on rat mGlu1 and mGlu5 are assessed by using calcium mobilization and measuring the glutamate concentration-response relationship in the presence and absence of 10 μM VU0364770. Using a double-addition protocol, VU0364770 is added to the cells, followed 2.5 min later by a full concentration-response of glutamate. Shifts of the concentration-response relationship are used to assess potential potentiator (left shift of more than 2-fold) or antagonist (right shift of more than 2-fold or depression of the maximum response by at least 75%) activity of VU0364770. Compounds are further assessed for mGlu5 antagonist activity by performing a full concentration-response curve, starting at 30 μM and serially diluted it by using 1:3 dilutions, in the presence of an EC80 concentration of glutamate[1]. |
| Animal Admin | Rats[1] Adult male Sprague-Dawley rats, weighing 250 to 300 g, are used. Rat are examined for catalepsy 30 min after the administration of either VU0364770 (1-56.6 mg/kg s.c.), VU0364772 (1-56.6 mg/kg s.c.), A2A antagonist (56.6 mg/kg p.o.), Preladenant (0.03-30 mg/kg p.o.), or vehicle. In the interaction studies rats ate administered VU0364770 (10 or 30 mg/kg) + vehicle, VU0364770 (10 or 30 mg/kg)+Preladenant (0.1-1 mg/kg), or vehicle+Preladenant (0.1-1 mg/kg) 30 min before testing. |
| References |
| Molecular Formula | C12H9ClN2O |
|---|---|
| Molecular Weight | 232.66600 |
| Exact Mass | 232.04000 |
| PSA | 45.48000 |
| LogP | 3.37130 |
| Storage condition | -20°C |
| HS Code | 2933399090 |
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|
~97%
61350-00-3 |
| Literature: Engers, Darren W.; Niswender, Colleen M.; Weaver, C. David; Jadhav, Satyawan; Menon, Usha N.; Zamorano, Rocio; Conn, P. Jeffrey; Lindsley, Craig W.; Hopkins, Corey R. Journal of Medicinal Chemistry, 2009 , vol. 52, # 14 p. 4115 - 4118 |
| HS Code | 2933399090 |
|---|---|
| Summary | 2933399090. other compounds containing an unfused pyridine ring (whether or not hydrogenated) in the structure. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0% |