VU6053371
VU6053371 (BI03738809) is a first-in-class (FIC), selective, orally active, and brain-penetrant metabotropic glutamate receptor subtype 3 (mGlu3) positive allosteric modulator (PAM) with EC50s of 103 nM and 112 nM for human and rat mGlu3. VU6053371 exhibits selectivity for mGlu3 over other mGlu receptor subtypes. VU6053371 exhibits pro-cognitive effects in mouse models. VU6053371 can be used in research schizophrenia, Alzheimer’ s disease and other forms of dementia and cognitive impairment.
商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 分子式: C19H19FN4O2S
- 分子量:386.44
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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生物活性
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化学情報
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
生物活性
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mGluR3 103 nM (EC50, human) |
mGluR3 112 nM (EC50, rat) |
VU6053371 (compound 13I) is an equipotent mGlu3 PAM for both human (EC50 = 113 nM, 61% Glu Max) and rat (EC50 = 112 nM, 58% Glu Max) and, importantly, inactive (EC50 > 30 μM) for both human and rat mGlu2[1].
VU6053371 is metabolized in mouse, rat, minipig, dog, monkey, and human hepatocytes, with the oxidation product M402A being the most abundant metabolite, whereas the glutathione conjugate M562 is not represented in any species tested[1].
VU6053371 displays a good CYP450 profile (IC50s: 3A4 (>30 μM), 2D6 (>30 μM), 2C9 (16 μM), 1A2 (26 μM)), even against 1A2[1].
VU6053371 shows no time-dependent CYP450 inhibition at 3A4, is negative in the mini-AMES (with and without S9), and exhibits no CV/QT concern in a functional EP hERG assay (IC50 > 30 μM)[1].
VU6053371 (10 μM 1 h) leeds to the identification of a GSH conjugate (M691) and forms 5.9% of this adduct after incubation in fortified microsomes with human liver cytosol and GSH[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
VU6053371 (1-10 mg/kg; p.o.) affords a robust PK/PD relationship for efficacy in the NOR paradigm when unbound brain exposures are at or above the rat mGlu3 PAM EC50[1].
VU6053371 (100-300mg/kg; p.o.; twice a day; 9 days) exhibits an unfavorable toxicological profile in rats[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:The mGlu2 and mGlu3 knockout mice with LY379268[1].
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Dosage:10 μM
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Administration:
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Result:Potentiated group II agonist LY379268-induced LTD in mouse PFC slices, further confirmed earlier work with KO mice and selective NAMs.
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Animal Model:Male rats[1].
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Dosage:30 mg/kg, 100 mg/kg, 300 mg/kg
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Administration:p.o.; twice a day; 9 days
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Result:Demonstrated systemic drug exposure in all animals treated with VU6053371.
Developed significant clinical symptoms accompanied by a decrease in body temperature at a dose of 100-300 mg/kg.
Showed mildly to moderately reduced reticulocyte counts on day 8 at a dose of 30-300 mg/kg.
Had moderately lower white blood cell, lymphocyte, and monocyte counts at a single dose of 300 mg/kg compared to controls.
Showed diffuse bone marrow hypocellularity at 100 mg/kg/dose.
Exhibited mild multifocal inflammatory foci in the myocardium, not limited to a specific heart region at all high-dose males.
Showed diffuse bone marrow hypocellularity at 100 mg/kg/dose.
Exhibited mild multifocal inflammatory foci in the myocardium, with myocardial fiber injury confined to areas of inflammatory infiltration,and no fibrosis or no abnormal cardiac Troponin/cleaved Caspase-3 IHC signals at high-dose.
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Animal Model:Male Sprague-Dawley rats subjected to habituation training in NOR arenas[1].
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Dosage:1 mg/kg, 3 mg/kg, 10 mg/kg
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Administration:p.o.;single dose
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Result:Dose-dependently enhanced recognition memory in rats with a minimum effective dose (MED) of 3 mg/kg PO and a near maximum response at 10 mg/kg PO.
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Animal Model:Male Sprague-Dawley rats (PO 0.5% natrosol/0.015% Tween 80 in water, 30 min) [1].
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Dosage:1 mg/kg, 3 mg/kg, 10 mg/kg
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Administration:p.o.;single dose
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Result:Achieved unbound brain levels of 151 nM (~1.35-fold the rat mGlu3 PAM EC50) at the 3 mg/kg PO MED, and produced maximal efficacy at 10 mg/kg PO (free brain = 385 nM, ~3.43-fold the EC50.
化学情報
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分子量 386.44
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分子式 C19H19FN4O2S
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SMILES
FC1=CC(C2=C(C)SC(NC3=CN=C(C(C)(C)O)N=C3)=C2C(N)=O)=CC=C1
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別名
BI03738809
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
VU6053371 関連分類
HY-184475 関連分類
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