Size | Price | Stock | Qty |
---|---|---|---|
5mg |
|
||
10mg |
|
||
25mg |
|
||
50mg |
|
||
100mg |
|
||
250mg |
|
||
500mg |
|
||
Other Sizes |
|
Purity: ≥98%
JNJ-46778212 (also known as VU 0409551) is a novel, potent, orally bioavailable metabotropic glutamate receptor subtype 5 (mGlu5) positive allosteric modulator (PAMs) with an EC50 of 260 nM. JNJ-46778212 demonstrates a unique stimulus bias and preferentially enhances mGlu5 coupling to Gαq-mediated signaling in the rat hippocampal regions, but not mGlu5 modulation of NMDAR currents or NMDAR-dependent synaptic plasticity. On the basis of its robust in vitro potency and in vivo efficacy in multiple preclinical models of multiple domains of schizophrenia, coupled with a good DMPK profile and an acceptable therapeutic window, JNJ-46778212 was selected as a candidate for further development.
Targets |
mGlu5 Receptor ( EC50 = 260 nM )
|
---|---|
ln Vivo |
JNJ-46778212 exhibits good CNS penetration in oral brain/plasma studies[1]. In hippocampus slices taken from SR−/− mice, JNJ-46778212 improves NMDAR function and restores long-term potentiation. When SR−/− mice receive JNJ-46778212, their deficits in multiple neuroplasticity signaling pathways are reversed, and their contextual fear memory is improved[2].
|
Animal Protocol |
Mice: For five days, SR−/− mice are given intraperitoneal (i.p.) injections of either VU0409551 (10 mL/kg) or a vehicle (20 % hydroxypropyl β-cyclodextran). In the in vivo pharmacokinetic and dose-finding experiments, VU0409551 (10 and 30 mg/kg) or vehicle is administered to WT mice (n = 5–6/dose). WT mice receive vehicle for the SR−/− mice reversal studies, while SR−/− mice receive either vehicle or VU0409551 (30 mg/kg). On day 5, two hours after the last injection, all mice are euthanized[1].
|
References |
Molecular Formula |
C20H17FN2O3
|
---|---|
Molecular Weight |
352.358988523483
|
Exact Mass |
352.12
|
Elemental Analysis |
C, 68.17; H, 4.86; F, 5.39; N, 7.95; O, 13.62
|
CAS # |
1363281-27-9
|
Appearance |
Solid powder
|
SMILES |
C1CN(CC2=C1N=C(O2)COC3=CC=CC=C3)C(=O)C4=CC=C(C=C4)F
|
InChi Key |
QUZLMKNNIUSREV-UHFFFAOYSA-N
|
InChi Code |
InChI=1S/C20H17FN2O3/c21-15-8-6-14(7-9-15)20(24)23-11-10-17-18(12-23)26-19(22-17)13-25-16-4-2-1-3-5-16/h1-9H,10-13H2
|
Chemical Name |
(4-fluorophenyl)-[2-(phenoxymethyl)-6,7-dihydro-4H-[1,3]oxazolo[5,4-c]pyridin-5-yl]methanone
|
Synonyms |
JNJ-46778212; JNJ 46778212; JNJ46778212; VU0409551; VU-0409551; VU 0409551
|
HS Tariff Code |
2934.99.9001
|
Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
Solubility (In Vitro) |
DMSO: ~100 mg/mL (~283.8 mM)
|
---|
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.8380 mL | 14.1900 mL | 28.3801 mL | |
5 mM | 0.5676 mL | 2.8380 mL | 5.6760 mL | |
10 mM | 0.2838 mL | 1.4190 mL | 2.8380 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.
Chemical evolution of a series of (2(phenoxymethyl)-6,7-dihydrooxazolo[5,4-c]pyridine-5(4H)-yl(aryl)methanones17that provided the first mGlu5PAM clinical candidate.ACS Med Chem Lett.2015 May 20;6(6):716-20. th> |
---|
Molecular pharmacological profile of17a. (A) Enhanced calcium release induced by suboptimal concentrations of glutamate (EC20), the PAM CRC, with an EC50for potentiation of 260 nM. (B) Analogue17ainduces a 10-fold leftward shift of the glutamate CRC. (C) Binding study with [3H]-mPEPy, confirming an MPEP sight PAM (Human IC50= 4.37 μM, 82%). (D) mGlu selectivity data (fold-shift at 10 μM) showing that17ais highly selective for mGlu5. Each data point represents the mean ± SD (n= 3). td> |
Analogue17ahas antipsychotic-like activity in rats and dose-dependently (3–56.6 mg/kg, po) reverses AHL.#,*,∧p< 0.05 vs VAMP group, Dunnett’s test.ACS Med Chem Lett.2015 May 20;6(6):716-20. td> |