VU6053371
Based on 1 Customer Validation
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.
For research use only. We do not sell to patients.
- Formula: C19H19FN4O2S
- Molecular Weight:386.44
-
Storage:
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]
-
Biological Activity
-
Chemical Information
-
Solvent & Solubility
- Protocols
- Purity & Documentation
- References
-
Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
mGluR3 103 nM (EC50, human) |
mGluR3 112 nM (EC50, rat) |
In Vitro
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.
Parmacokinetics
In Vivo
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.
-
Animal Model:Male rats[1].
-
Dosage:30 mg/kg, 100 mg/kg, 300 mg/kg
-
Administration:p.o.; twice a day; 9 days
-
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.
-
Animal Model:Male Sprague-Dawley rats subjected to habituation training in NOR arenas[1].
-
Dosage:1 mg/kg, 3 mg/kg, 10 mg/kg
-
Administration:p.o.;single dose
-
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.
-
Animal Model:Male Sprague-Dawley rats (PO 0.5% natrosol/0.015% Tween 80 in water, 30 min) [1].
-
Dosage:1 mg/kg, 3 mg/kg, 10 mg/kg
-
Administration:p.o.;single dose
-
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.
Chemical Information
-
Molecular Weight 386.44
-
Formula C19H19FN4O2S
-
SMILES
FC1=CC(C2=C(C)SC(NC3=CN=C(C(C)(C)O)N=C3)=C2C(N)=O)=CC=C1
-
Synonyms
BI03738809
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Solvent & Solubility
In Vitro:
DMSO : ≥ 100 mg/mL (258.77 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Purity & Documentation
References
Complete Stock Solution Preparation Table
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.5877 mL | 12.9386 mL | 25.8772 mL | 64.6931 mL |
| 5 mM | 0.5175 mL | 2.5877 mL | 5.1754 mL | 12.9386 mL | |
| 10 mM | 0.2588 mL | 1.2939 mL | 2.5877 mL | 6.4693 mL | |
| 15 mM | 0.1725 mL | 0.8626 mL | 1.7251 mL | 4.3129 mL | |
| 20 mM | 0.1294 mL | 0.6469 mL | 1.2939 mL | 3.2347 mL | |
| 25 mM | 0.1035 mL | 0.5175 mL | 1.0351 mL | 2.5877 mL | |
| 30 mM | 0.0863 mL | 0.4313 mL | 0.8626 mL | 2.1564 mL | |
| 40 mM | 0.0647 mL | 0.3235 mL | 0.6469 mL | 1.6173 mL | |
| 50 mM | 0.0518 mL | 0.2588 mL | 0.5175 mL | 1.2939 mL | |
| 60 mM | 0.0431 mL | 0.2156 mL | 0.4313 mL | 1.0782 mL | |
| 80 mM | 0.0323 mL | 0.1617 mL | 0.3235 mL | 0.8087 mL | |
| 100 mM | 0.0259 mL | 0.1294 mL | 0.2588 mL | 0.6469 mL |
VU6053371 Related Classifications
HY-184475 Related Classifications
Powered by Bioz