| Chemical Properties | Back Directory | [Boiling point ]
405.1±24.0 °C(Predicted) | [density ]
1.130±0.06 g/cm3(Predicted) | [storage temp. ]
-20°C | [solubility ]
DMSO: 5mg/mL, clear (warmed) | [form ]
powder | [pka]
-0.05±0.40(Predicted) | [color ]
white to beige |
| Hazard Information | Back Directory | [Uses]
(±)-ADX 71743 is a potent and selective negative allosteric modulator of metabotropic glutamate receptor 7 mGlu7. | [Biological Activity]
ADX71743 is a brain-penetrantselective and potent negative allosteric modulator of metabotropic glutamate receptor 7 (mGlu7). In one study ADX71743 exhibited an anxiolytic-like profile in r at and mouse models without causing impairment of locomotor activity. In another study it induced absence epileptic seizures and lethargy.''ADX71743 is known to negatively regulate the effect of mGlu7 (metabotropic glutamate receptor subtype 7)which is associated with a number of anxiety disorders. | [Enzyme inhibitor]
This brain-penetrant mGlu7 allosteric negative modulator (FW = 269.34 g/mol; CAS 1431641-29-0; Solubility: 100 mM in DMSO), also named 6- (2,4-dimethylphenyl)-2-ethyl-6,7-dihydro-4(5H)-benzoxazolone, potently and selectively targets the metabotropic glutamate receptor-7, itself a promising novel target for treatment of anxiety, post-traumatic stress disorder, depression, drug abuse, and schizophrenia. When tested in vitro, Schild plot analysis and reversibility tests at the target confirmed the NAM properties of the compound and attenuation of L-(+)-2-amino-4- phosphonobutyric acid (or L-AP4) -induced synaptic depression confirmed activity at the native receptor. When tested in vitro, ADX-71743 gives a IC50 value versus EC80 of glutamate = 22 nM at human mGlu7 in a 3’,5’- cyclic-AMP assay, with IC50 values versus EC80 of L-AP4 are 63 and 125 nM at human mGlu7 in Ca2+ and cAMP assays respectively; IC50 value versus EC80 of L-AP4 = 88 nM at rmGlu7 in a Ca2+assay). Selective for mGlu7 over all other mGlu receptor subtypes and a panel of relevant GPCRs. Exhibits an anxiolytic-like profile in vivo. The Schild plot experiments clearly indicate the noncompetitive nature of ADX71743 inhibition, whereas simple wash experiments seem to indicate that its binding to the receptor is readily reversible. Other Targets: When tested for its action at other mGlu-expressing cells in series of FLIPR experiments, ADX71743 showed no detectable activity (either agonist or allosteric effects) in cell lines expressing hmGlu3, hmGlu4, rmGlu5, hmGlu6, and hmGlu8. A negligible inhibition of rmGlu1 (32% at 30 μM) and a weak positive allosteric modulator effect on hmGlu2 (EC50 = 11 μM) was measured. When further tested in a functional GPCR screen against 27 targets in agonist and antagonist modes, ADX71743 exhibited no stimulation or inhibition above 27% was observed. | [in vivo]
ADX71743 (50, 100, 150 mg/kg; SC) results in robust reductions in numbers of buried marbles to near maximal levels at lower doses (50 and 100 mg/kg)[2].
ADX71743 (12.5, 100 mg/kg for mice and 100 mg/kg for rat; SC) has a T1/2 of 0.68, 0.40 hours, a Cmax of 1380, 12766 ng/ml of 12.5 mg/kg and 100 mg/kg in mice[2].
| Animal Model: | Adult male C57Bl6/J mice (24-30 g)[2] | | Dosage: | 50, 100, 150 mg/kg | | Administration: | SC | | Result: | Resulted in robust reductions in numbers of buried marbles to near maximal levels at lower doses (50 and 100 mg/kg).
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| Animal Model: | Adult male C57Bl6/J mice (24-30 g) and Sprague-Dawley rats (250-350 g)[2] | | Dosage: | 12.5, 100 mg/kg for mice and 100 mg/kg for rat (Pharmacokinetic Analysis) | | Administration: | SC | | Result: | Had a T1/2 of 0.68, 0.40 hours, a Cmax of 1380, 12766 ng/ml of 12.5 mg/kg and 100 mg/kg in mice.
Had a T1/2 of 1.5 hours, a Cmax of 16800 ng/ml of 100 mg/kg in rat.
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| [IC 50]
mGlu7 |
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| Company Name: |
BOC Sciences
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https://www.bocsci.com |
| Company Name: |
Energy Chemical
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http://www.energy-chemical.com |
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R&D Systems, Inc
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18003437475 18003437475 |
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www.rndsystems.com |
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Merck KGaA
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21-20338288 |
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www.sigmaaldrich.cn |
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MedChemExpress
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021-58955995 |
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www.medchemexpress.com |
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