Synonym
LY-2365109 free base; LY 2365109 ; LY-2365109 ; LY2365109;
IUPAC/Chemical Name
N-(2-(4-(benzo[d][1,3]dioxol-5-yl)-2-(tert-butyl)phenoxy)ethyl)-N-methylglycine
InChi Key
FKPLJWGRBCQLTL-UHFFFAOYSA-N
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)
SMILES Code
O=C(O)CN(CCOC1=CC=C(C2=CC=C(OCO3)C3=C2)C=C1C(C)(C)C)C
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
LY2365109 is a glycine transporter 1 (GlyT1) inhibitor (IC50 values are 15.8 and > 30 000 nM at GlyT1 and GlyT2 respectively).
In vivo activity:
In support of a role of dysfunctional glycine signaling in the pathophysiology of epilepsy, both the genetic deletion of GlyT1 in hippocampus and the GlyT1 inhibitor LY2365109 increased seizure thresholds in mice. Importantly, chronic seizures in the mouse model of TLE were robustly suppressed by systemic administration of the GlyT1 inhibitor LY2365109.
Reference: Neuropharmacology. 2015 Dec;99:554-65. https://pubmed.ncbi.nlm.nih.gov/26302655/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
385.46
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Shen HY, van Vliet EA, Bright KA, Hanthorn M, Lytle NK, Gorter J, Aronica E, Boison D. Glycine transporter 1 is a target for the treatment of epilepsy. Neuropharmacology. 2015 Dec;99:554-65. doi: 10.1016/j.neuropharm.2015.08.031. Epub 2015 Aug 21. PMID: 26302655; PMCID: PMC4655139.
2. Perry KW, Falcone JF, Fell MJ, Ryder JW, Yu H, Love PL, Katner J, Gordon KD, Wade MR, Man T, Nomikos GG, Phebus LA, Cauvin AJ, Johnson KW, Jones CK, Hoffmann BJ, Sandusky GE, Walter MW, Porter WJ, Yang L, Merchant KM, Shannon HE, Svensson KA. Neurochemical and behavioral profiling of the selective GlyT1 inhibitors ALX5407 and LY2365109 indicate a preferential action in caudal vs. cortical brain areas. Neuropharmacology. 2008 Oct;55(5):743-54. doi: 10.1016/j.neuropharm.2008.06.016. Epub 2008 Jun 17. PMID: 18602930.
In vivo protocol:
1. Shen HY, van Vliet EA, Bright KA, Hanthorn M, Lytle NK, Gorter J, Aronica E, Boison D. Glycine transporter 1 is a target for the treatment of epilepsy. Neuropharmacology. 2015 Dec;99:554-65. doi: 10.1016/j.neuropharm.2015.08.031. Epub 2015 Aug 21. PMID: 26302655; PMCID: PMC4655139.
2. Perry KW, Falcone JF, Fell MJ, Ryder JW, Yu H, Love PL, Katner J, Gordon KD, Wade MR, Man T, Nomikos GG, Phebus LA, Cauvin AJ, Johnson KW, Jones CK, Hoffmann BJ, Sandusky GE, Walter MW, Porter WJ, Yang L, Merchant KM, Shannon HE, Svensson KA. Neurochemical and behavioral profiling of the selective GlyT1 inhibitors ALX5407 and LY2365109 indicate a preferential action in caudal vs. cortical brain areas. Neuropharmacology. 2008 Oct;55(5):743-54. doi: 10.1016/j.neuropharm.2008.06.016. Epub 2008 Jun 17. PMID: 18602930.
1: Perry KW, Falcone JF, Fell MJ, Ryder JW, Yu H, Love PL, Katner J, Gordon KD, Wade MR, Man T, Nomikos GG, Phebus LA, Cauvin AJ, Johnson KW, Jones CK, Hoffmann BJ, Sandusky GE, Walter MW, Porter WJ, Yang L, Merchant KM, Shannon HE, Svensson KA. Neurochemical and behavioral profiling of the selective GlyT1 inhibitors ALX5407 and LY2365109 indicate a preferential action in caudal vs. cortical brain areas. Neuropharmacology. 2008 Oct;55(5):743-54. doi: 10.1016/j.neuropharm.2008.06.016. Epub 2008 Jun 17. PMID: 18602930.
2: Shen HY, van Vliet EA, Bright KA, Hanthorn M, Lytle NK, Gorter J, Aronica E, Boison D. Glycine transporter 1 is a target for the treatment of epilepsy. Neuropharmacology. 2015 Dec;99:554-65. doi: 10.1016/j.neuropharm.2015.08.031. Epub 2015 Aug 21. PMID: 26302655; PMCID: PMC4655139.
3: Zhang J, Wu J, Toyohara J, Fujita Y, Chen H, Hashimoto K. Pharmacological characterization of [³H]CHIBA-3007 binding to glycine transporter 1 in the rat brain. PLoS One. 2011;6(6):e21322. doi: 10.1371/journal.pone.0021322. Epub 2011 Jun 23. PMID: 21731704; PMCID: PMC3121759.
