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LY2389575

Alias: LY 2389575 LY2389575 LY-2389575
Cat No.:V7417 Purity: ≥98%
LY2389575 HCl is a selective and noncompetitive mGlu3 negative allosteric modulator (NAM) with IC50 of 190 nM.
LY2389575
LY2389575 Chemical Structure CAS No.: 885104-09-6
Product category: New1
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
5mg
10mg
50mg
Other Sizes
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Product Description
LY2389575 HCl is a selective and noncompetitive mGlu3 negative allosteric modulator (NAM) with IC50 of 190 nM. LY2389575 HCl can induce an increase in Mrc1 levels. LY2389575 HCl can also amplify the toxicity of amyloid beta (Aβ) and may be utilized in Alzheimer's disease (AD) research.
Biological Activity I Assay Protocols (From Reference)
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C15H16BRCL3N4
Molecular Weight
438.57
Exact Mass
435.962
CAS #
885104-09-6
Related CAS #
885102-71-6;885104-09-6 (HCl);
PubChem CID
11503054
Appearance
White to light yellow solid powder
Hydrogen Bond Donor Count
2
Hydrogen Bond Acceptor Count
4
Rotatable Bond Count
4
Heavy Atom Count
23
Complexity
354
Defined Atom Stereocenter Count
1
SMILES
C1CN(C[C@H]1NCC2=C(C=C(C=C2)Cl)Cl)C3=NC=C(C=N3)Br.Cl
InChi Key
IRIBLLOEUZMCQY-ZOWNYOTGSA-N
InChi Code
InChI=1S/C15H15BrCl2N4.ClH/c16-11-7-20-15(21-8-11)22-4-3-13(9-22)19-6-10-1-2-12(17)5-14(10)18;/h1-2,5,7-8,13,19H,3-4,6,9H2;1H/t13-;/m0./s1
Chemical Name
(3S)-1-(5-bromopyrimidin-2-yl)-N-[(2,4-dichlorophenyl)methyl]pyrrolidin-3-amine;hydrochloride
Synonyms
LY 2389575 LY2389575 LY-2389575
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 Data
Solubility (In Vitro)
DMSO : ~100 mg/mL (~228.01 mM)
MEthanol : ~8.33 mg/mL (~18.99 mM)
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.70 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 (5.70 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (5.70 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 2.2801 mL 11.4007 mL 22.8014 mL
5 mM 0.4560 mL 2.2801 mL 4.5603 mL
10 mM 0.2280 mL 1.1401 mL 2.2801 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.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

  • Calculate the Mass of a compound required to prepare a solution of known volume and concentration
  • Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
  • Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume
An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
  • To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

  • Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
  • Click the “Calculate” button
  • The answer appears in the Volume (to add to vial) box
In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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.

Biological Data
  • Pharmacological mGlu3 receptor blockade and microglial reactivity in response to inflammatory stimulation in vitro. a, b Microglial cells sorted from P4 pups were stained with Iba1 (green) and DAPI (blue) under basal conditions ± LY 2389575 (5 μM). Representative photomicrographs at × 40 magnification are shown in a (scale bar = 50 μm). The cell area, cell perimeter, and cell circularity were assessed in b (mean cell number, 162 ± 10). Data (mean ± SEM). Unpaired t test; **p < 0.01. c, d mRNA expression of pro-inflammatory (c) and anti-inflammatory/immune-regulatory (d) markers in microglial cells sorted from P4 pups cultured under basal or pro-inflammatory (IL-1β + INFγ) conditions ± LY 2389575 (5 μM). The data (mean ± SEM) are relative to the gene expression under basal CTRL conditions. One-way ANOVA followed by the Newman-Keuls multiple comparison test; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.001 effect of LY 2389575; $p < 0.05, $$p < 0.01, $$$p < 0.001, $$$$p < 0.0001 effect of IL-1β + INFγ. e, f Microglial cells sorted from P7 pups were stained with Iba1 (green) and DAPI (blue) under basal conditions ± LY 2389575 (5 μM). Representative photomicrographs at × 40 magnification are shown in e (scale bar = 50 μm). The cell area, cell perimeter, and cell circularity were assessed in f (mean cell number, 162 ± 10). Data (mean ± SEM). Unpaired t test *p < 0.01, **p < 0.01. g, h mRNA expression of pro-inflammatory.[2]. Zinni M, et al. mGlu3 receptor regulates microglial cell reactivity in neonatal rats. J Neuroinflammation. 2021 Jan 6;18(1):13.
  • Effects of pharmacological mGlu3 receptor modulation and Grm3 knock-down on microglial Ccl9 expression in vitro. a, c mRNA expression of Ccl9 under the pro-inflammatory condition (IL-1β + IFNγ) in the presence of LY 379268 (1 μM) + Ro 64-5229 (25 μM) in CTRL and LPD/IL-1β cultured microglia at P4 (a) and at P7 (c). Data (mean ± SEM) are relative to the gene expression under basal CTRL conditions. Two-way ANOVA followed by the Newman-Keuls multiple comparison; *p < 0.05, ***p < 0.001 effect of LY 379268 + Ro 64-5229; $p < 0.05, $$p < 0.01, $$$p < 0.001 effect of IL-1β + IFNγ; #p < 0.05, ###p < 0.001 effect of LPD/IL-1β. b, d mRNA expression of Ccl9 in microglial cells sorted from P4 (b) and P7 (d) rat pups cultured under basal or pro-inflammatory (IL-1β + INFγ) conditions ± LY 2389575 (5 μM). The data (mean ± SEM) are relative to the gene expression under basal CTRL conditions. One-way ANOVA followed by the Newman-Keuls multiple comparison test; **p < 0.01, ***p < 0.001, ****p < 0.0001 effect of LY 2389575; $p < 0.05 effect of IL-1β + INFγ. e Ccl9 mRNA expression in response to SCR and Grm3 siRNA (50 nM). Data (mean ± SEM) are relative to the mRNA expression for the respective SCR. Unpaired t test; ****p < 0.0001. f Pearson’s correlation between Grm3 expression and Ccl9 48 h after transfection with siGrm3 (50 nM).[2]. Zinni M, et al. mGlu3 receptor regulates microglial cell reactivity in neonatal rats. J Neuroinflammation. 2021 Jan 6;18(1):13.
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