VU 0364770
Modify Date: 2025-08-25 18:59:18
VU 0364770 structure
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Common Name | VU 0364770 | ||
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| CAS Number | 61350-00-3 | Molecular Weight | 232.66600 | |
| Density | N/A | Boiling Point | N/A | |
| Molecular Formula | C12H9ClN2O | Melting Point | N/A | |
| MSDS | N/A | Flash Point | N/A | |
Use of VU 0364770VU0364770 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 |
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| Synonym | More Synonyms |
| 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. |
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| 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 |
| InChIKey | SUYUTNCKIOLMAJ-UHFFFAOYSA-N |
| SMILES | O=C(Nc1cccc(Cl)c1)c1ccccn1 |
| Storage condition | -20°C |
| HS Code | 2933399090 |
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~97%
VU 0364770 CAS#: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 |
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| 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% |
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Name: Discovery of Small Molecules to Inhibit Human Cytomegalovirus Nuclear Egress
Source: ICCB-Longwood/NSRB Screening Facility, Harvard Medical School
Target: HCMV UL50
External Id: HMS1262
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Name: Activity at rat mGluR4 expressed in HEK293 cells coexpressing Gqi5 protein assessed a...
Source: ChEMBL
Target: Metabotropic glutamate receptor 4
External Id: CHEMBL1034760
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Name: Activity at rat mGluR4 receptor expressed in HEK293 cells assessed as effect on thall...
Source: ChEMBL
Target: Metabotropic glutamate receptor 4
External Id: CHEMBL1034758
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Name: Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VER...
Source: ChEMBL
Target: Severe acute respiratory syndrome coronavirus 2
External Id: CHEMBL4513082
|
|
Name: Activity at human mGluR4 expressed in CHO cells coexpressing Gqi5 protein assessed as...
Source: ChEMBL
Target: Metabotropic glutamate receptor 4
External Id: CHEMBL1034759
|
|
Name: Hit confirmation of the active molecules of the enzymatic assay of human HDAC6 with c...
Source: ChEMBL
Target: Histone deacetylase 6
External Id: CHEMBL4808151
|
|
Name: ASTRAZENECA: Octan-1-ol/water (pH7.4) distribution coefficent measured by a shake fl...
Source: ChEMBL
Target: N/A
External Id: CHEMBL3301363
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|
Name: Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Cac...
Source: ChEMBL
Target: Severe acute respiratory syndrome coronavirus 2
External Id: CHEMBL4303805
|
|
Name: Determination of IC50 values for inhibition of enzymatic assay of human HDAC6 with cu...
Source: ChEMBL
Target: Histone deacetylase 6
External Id: CHEMBL4808152
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|
Name: SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response f...
Source: ChEMBL
Target: Replicase polyprotein 1ab
External Id: CHEMBL4495582
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| VU0364770 |