LY3020371 is a potent and specific glutamate receptor (mGluR2/3) antagonist (inhibitor) with Kis of 5.26 and 2.50 nM for hmGluR2 and hmGluR3, respectively. LY3020371 may be utilized to study depression.

Physicochemical Properties

Molecular Formula	C15H15F2NO5S
Molecular Weight	359.345110177994
Exact Mass	359.063
CAS #	1377615-75-2
Related CAS #	LY3020371 hydrochloride;1377615-44-5
PubChem CID	69669747
Appearance	Typically exists as solid at room temperature
LogP	-1.9
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	5
Heavy Atom Count	24
Complexity	552
Defined Atom Stereocenter Count	6
SMILES	C1=CC(=C(C=C1SC[C@@H]2[C@H]([C@H]3[C@@H]([C@H]3[C@@]2(C(=O)O)N)C(=O)O)O)F)F
InChi Key	PVCLSZDVATUGHR-XJDZXMJWSA-N
InChi Code	InChI=1S/C15H15F2NO5S/c16-7-2-1-5(3-8(7)17)24-4-6-12(19)9-10(13(20)21)11(9)15(6,18)14(22)23/h1-3,6,9-12,19H,4,18H2,(H,20,21)(H,22,23)/t6-,9+,10+,11+,12-,15+/m1/s1
Chemical Name	(1S,2R,3S,4S,5R,6R)-2-amino-3-[(3,4-difluorophenyl)sulfanylmethyl]-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid
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)

Biological Activity

Targets	hmGluR2 5.26 nM (Ki) hmGluR3 2.50 nM (Ki)
ln Vitro	A high affinity binding of the mGlu2/3 agonist ligand [3H]-459477 is competitively displaced by LY3020371 (0.1 nM-100 μM)[1]. Forskolin-stimulated cAMP generation in cells expressing recombinant human mGlu2 (IC50=16.2 nM) and mGlu3 (IC50=6.21 nM) receptors is inhibited by DCG-IV, although LY3020371 (0.1 nM-100 μM) prevents this effect[1]. The concentration-dependent antagonistic effects of LY3020371 (0.3-30000 nM) on LY379268-inhibited cAMP production are demonstrated[1]. With an IC50 of 86 nM, LY3020371 (1-10000 nM) restores the K+-evoked, LY379268-suppressed glutamate release[1]. With an IC50 of 33.9 nM, LY3020371 (0.3-10000 nM) completely blocks the LY379268-suppressed response in a concentration-dependent manner[1].
ln Vivo	In the ventral tegmental region (VTA) of rats, LY3020371 (0.3-3 mg/kg, a single IV) dramatically increases the amount of spontaneously activated dopamine cells[2]. Rat anterior cingulate cortex (ACC) tissue oxygen levels are dose-dependently increased by LY3020371 (1–10 mg/kg, ip once weekly for 5 weeks)[2]. In the medial prefrontal cortex of rats that are free to move around, LY3020371 (10 mg/kg, one intraperitoneal shot) enhances monoamine efflux[2]. Rats' cumulative waking time is increased by LY3020371 (1–30 mg/kg, a single intravenous) in a dose- and time-dependent way without experiencing rebound hypersomnolence[2]. Rat forced-swim assay: LY3020371 (0.1–10 mg/kg, single intravenous) reduces the amount of time rats are immobile[2].
Animal Protocol	Animal/Disease Models: Male SD (Sprague-Dawley) rats (230-350 g)[1] Doses: 0.3, 1, 3 mg/kg Route of Administration: Iv daily 5 days per week for 2 weeks Experimental Results: Increased the number of actively firing dopamine neurons in the VTA of anesthetized rats.
References	[1]. Witkin JM, In vitro pharmacological and rat pharmacokinetic characterization of LY3020371, a potent and selective mGlu 2/3 receptor antagonist. Neuropharmacology. 2017 Mar 15;115:100-114. [2]. Comparative Effects of LY3020371, a Potent and Selective Metabotropic Glutamate (mGlu) 2/3 Receptor Antagonist, and Ketamine, a Noncompetitive N-Methyl-d-Aspartate Receptor Antagonist in Rodents: Evidence Supporting the Use of mGlu2/3 A. [3]. mGlu2/3 receptor antagonism: A mechanism to induce rapid antidepressant effects without ketamine-associated side-effects. Pharmacol Biochem Behav. 2020 Mar;190:172854.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.7828 mL	13.9140 mL	27.8280 mL
	5 mM	0.5566 mL	2.7828 mL	5.5656 mL
	10 mM	0.2783 mL	1.3914 mL	2.7828 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.