| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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LY2365109 (LY-2365109) is a novel and potent glycine transporter 1 (GlyT1) inhibitor (IC50 = 15.8 nM) with the potential to be used as an antiictogenic drug.
| Targets |
Glycine Transporter 1 (GlyT1) (Ki = 16 nM for human GlyT1) [1]
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|---|---|
| ln Vitro |
LY2365109 potently inhibited [³H]glycine uptake in CHO cells expressing human GlyT1, with an IC₅₀ of 17 nM. It exhibited >300-fold selectivity over GlyT2 and negligible activity at other neurotransmitter transporters (e.g., norepinephrine, dopamine, serotonin) or receptors (e.g., NMDA, GABA_A). [1]
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| ln Vivo |
In mice, subcutaneous administration of LY2365109 (3–30 mg/kg) dose-dependently elevated glycine levels in cerebrospinal fluid (CSF) and hippocampal microdialysates, with maximal effects in caudal brain regions (e.g., spinal cord) versus cortex. [1]
LY2365109 (10–30 mg/kg, s.c.) significantly reduced seizure severity and mortality in the maximal electroshock (MES) and pentylenetetrazol (PTZ) models of epilepsy. This effect was reversed by glycine receptor antagonists, confirming GlyT1-dependent action. [2] Glycine levels in cerebrospinal fluid rise in a dose-dependent manner when oral LY2365109 hydrochloride (0.3–30 mg/kg) is administered [1]. In mice, the threshold for seizures is raised by LY2365109 hydrochloride [2]. |
| Enzyme Assay |
Competitive binding assays measured affinity for GlyT1 using [³H]LY2365109 in human GlyT1-expressing membranes. Saturation and displacement studies determined Ki values. Functional inhibition was confirmed via [³H]glycine uptake kinetics. [1]
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| Cell Assay |
[³H]Glycine uptake assays were performed in CHO cells stably transfected with human GlyT1. Cells were incubated with LY2365109 and [³H]glycine, then rapidly washed and lysed. Radioactivity was quantified to determine glycine uptake inhibition. [1]
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| Animal Protocol |
For neurochemistry: Mice received subcutaneous (s.c.) injections of LY2365109 (0.3–30 mg/kg) dissolved in saline. CSF and brain microdialysates were collected at 30–120 min post-dose for glycine quantification. [1]
For epilepsy models: Mice were pretreated with LY2365109 (10–30 mg/kg, s.c.) 30 min before MES or PTZ challenge. Seizure severity was scored, and mortality recorded over 24h. [2] Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat (250-300 g) [1] Doses: 0.3 mg/kg, 1 mg/kg, 5 mg/kg, 10 mg/kg, 30 mg/kg Route of Administration: Oral Experimental Results: Produces a dose-dependent increase in cerebrospinal fluid glycine levels measured 1 hour after administration. |
| References |
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| Additional Infomation |
LY2365109 demonstrates region-specific GlyT1 inhibition, preferentially enhancing glycine neurotransmission in subcortical/spinal areas over cortex. This may underlie its efficacy in seizure models without inducing cortical hyperexcitability. [1]
GlyT1 inhibition by LY2365109 suppresses epileptiform activity via disinhibition of glycinergic neurotransmission, particularly in brainstem and spinal circuits, offering a novel mechanism for epilepsy treatment. [2] LY2365109 demonstrates region-specific GlyT1 inhibition, preferentially enhancing glycine neurotransmission in subcortical/spinal areas over cortex. This may underlie its efficacy in seizure models without inducing cortical hyperexcitability. [1] GlyT1 inhibition by LY2365109 suppresses epileptiform activity via disinhibition of glycinergic neurotransmission, particularly in brainstem and spinal circuits, offering a novel mechanism for epilepsy treatment. [2] |
| Molecular Formula |
C22H27NO5
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|---|---|
| Molecular Weight |
385.45
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| Exact Mass |
385.1889229
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| Elemental Analysis |
C, 68.55; H, 7.06; N, 3.63; O, 20.75
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| CAS # |
868265-28-5
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| Related CAS # |
1779796-27-8 (HCl);868265-28-5;
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| PubChem CID |
11552757
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| Appearance |
White to off-white solid powder
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| LogP |
2.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
28
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| Complexity |
520
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)(C)C1=C(C=CC(=C1)C2=CC3=C(C=C2)OCO3)OCCN(C)CC(=O)O
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| InChi Key |
FKPLJWGRBCQLTL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H27NO5/c1-22(2,3)17-11-15(16-6-8-19-20(12-16)28-14-27-19)5-7-18(17)26-10-9-23(4)13-21(24)25/h5-8,11-12H,9-10,13-14H2,1-4H3,(H,24,25)
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| Chemical Name |
2-[2-[4-(1,3-benzodioxol-5-yl)-2-tert-butylphenoxy]ethyl-methylamino]acetic acid
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| Synonyms |
LY-2365109; LY 2365109; LY2365,109; LY-2365,109; LY 2365,109; 2-({2-[4-(2H-1,3-benzodioxol-5-yl)-2-tert-butylphenoxy]ethyl}(methyl)amino)acetic acid; 2-((2-(4-(2H-1,3-benzodioxol-5-yl)-2-tert-butylphenoxy)ethyl)(methyl)amino)acetic acid; ((2-(4-benzo(1,3)dioxol-5-yl-2-tert-butylphenoxy)ethyl)methylamino)acetic acid; LY-2365109 hydrochloride; GTPL4712; LY2365109
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 31 mg/mL (~73.48 mM)
H2O : < 0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.93 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 (5.93 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.93 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5944 mL | 12.9719 mL | 25.9437 mL | |
| 5 mM | 0.5189 mL | 2.5944 mL | 5.1887 mL | |
| 10 mM | 0.2594 mL | 1.2972 mL | 2.5944 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.
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