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| 10mg |
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| 250mg |
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Purity: ≥98%
VU 0364770 (VU-0364770, VU0364770) is a potent positive allosteric modulator (PAM) of mGlu4 (metabotropic glutamate receptor 4) with anti-parkinsonian-like activity. It inhibits mGlu with an EC50 of 1.1 μM for human mGlu4. It exhibits little activity at 68 other receptors such as other mGlu subtypes. Positive allosteric modulators (PAMs) of metabotropic glutamate receptor 4 (mGlu₄), including N-phenyl-7-(hydroxyimino) cyclopropa[b]chromen-1a-carboxamide, can produce anti-parkinsonian-like effects in preclinical models of PD. VU0364770 produces efficacy alone and in combination with L-DOPA or an adenosine 2A antagonist in preclinical rodent models of Parkinson's disease.
| ln Vitro |
In recombinant systems, VU0364770 acts as a selective positive allosteric modulator of mGlu4. Strong PAM of several signaling pathways, VU0364770, increases the rat and human mGlu4 receptors' sensitivity to the endogenous agonist glutamate. VU0364770 raises the maximal response to glutamate from 100 to 227±17% and causes a concentration-dependent potentiation of the response to an EC20 concentration of glutamate with an EC50 of 1.1±0.2 μM. Full IC50 determinations are carried out for VU0364770 at the MAO-A and MAO-B isoforms due to concerns that this chemical scaffold may possess activity at MAO; these studies yield Kis of 8.5 and 0.72 μM for human MAO-A and human MAO-B, respectively. VU0364770 displays 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, when tested at a 10 μM concentration at each mGlu receptor (compare to the 16.5-fold left shift of the glutamate concentration-response for mGlu4 at 10 μM). VU0364770 shows 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 when further evaluated in a full concentration-response curve format (compare with the potency of VU0364770 on the rat mGlu4 receptor of 290±80}M)[1].
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| ln Vivo |
In animal models, VU0364770 shows appropriate pharmacokinetic characteristics for systemic administration. VU0364770 has a 2.92 L/kg volume of distribution and quickly leaves the systemic circulation (165 ml/min/kg) upon intravenous injection. The highly protein-bound ligand VU0364770 exhibits free fractions in rat and human plasma of 1.8% and 2.7%, respectively. Following systemic administration of a 10 mg/kg dosage, VU0364770 also exhibits a better pharmacokinetic profile in comparison to previously reported mGlu4 PAMs, with greater central penetration and a total brain-to-plasma ratio of more than 1. Haloperidol-induced cataleptic seizures are reversed in a dose-dependent manner by VU0364770. following subcutaneous administration (F6,69=8.04; p<0.001)[1].
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| References |
[1]. Jones CK, et al. The metabotropic glutamate receptor 4-positive allosteric modulator VU0364770 produces efficacy alone and in combination with L-DOPA or an adenosine 2A antagonist in preclinical rodent models of Parkinson's disease. J Pharmacol Exp Ther
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| Molecular Formula |
C12H9CLN2O
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| Molecular Weight |
232.67
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| CAS # |
61350-00-3
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| Related CAS # |
VU0364770 hydrochloride;1414842-70-8
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| SMILES |
O=C(C1=NC=CC=C1)NC2=CC=CC(Cl)=C2
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.74 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (10.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.2979 mL | 21.4897 mL | 42.9793 mL | |
| 5 mM | 0.8596 mL | 4.2979 mL | 8.5959 mL | |
| 10 mM | 0.4298 mL | 2.1490 mL | 4.2979 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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