Synonym
GSK2578215A; GSK-2578215A; GSK 2578215A; GSK257821A; GSK 257821A; GSK-257821A; GSK2578215-A;
IUPAC/Chemical Name
2-(benzyloxy)-5-(2-fluoropyridin-4-yl)-N-(pyridin-3-yl)benzamide
InChi Key
WCIGMFCFPXZRMQ-UHFFFAOYSA-N
InChi Code
InChI=1S/C24H18FN3O2/c25-23-14-19(10-12-27-23)18-8-9-22(30-16-17-5-2-1-3-6-17)21(13-18)24(29)28-20-7-4-11-26-15-20/h1-15H,16H2,(H,28,29)
SMILES Code
O=C(NC1=CC=CN=C1)C2=CC(C3=CC(F)=NC=C3)=CC=C2OCC4=CC=CC=C4
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, not in water
Shelf Life
>2 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:
GSK2578215A is a potent and highly selective LRRK2 inhibitor, which exhibits IC50s of around 10 nM against both wild-type LRRK2 and the G2019S mutant.
In vitro activity:
GSK2578215A induced oxidative stress as evidenced by the accumulation of 4-hydroxy-2-nonenal in SH-SY5Y cells.
Reference: Cell Death Dis. 2014 Aug 14;5(8):e1368. https://pubmed.ncbi.nlm.nih.gov/25118928/
In vivo activity:
Based on these pharmacokinetic properties, pharmacodynamic experiments examining inhibition of LRRK2 Ser910/Ser935 phosphorylation were conducted after intraperitoneal injection with 100 mg/kg of GSK2578215A to normal mice. This study observed complete Ser910 and Ser935 dephosphorylation of LRRK2 in the kidney and spleen, which also demonstrated similar potency relative to LRRK2-IN-1 (Fig. 5).
Reference: Bioorg Med Chem Lett. 2012 Sep 1;22(17):5625-9. https://pubmed.ncbi.nlm.nih.gov/22863203/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMF |
10.0 |
25.04 |
| DMSO |
44.7 |
112.00 |
| DMSO:PBS (pH 7.2) (1:1) |
0.5 |
1.25 |
| Ethanol |
1.0 |
2.50 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
399.43
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. Saez-Atienzar S, Bonet-Ponce L, Blesa JR, Romero FJ, Murphy MP, Jordan J, Galindo MF. The LRRK2 inhibitor GSK2578215A induces protective autophagy in SH-SY5Y cells: involvement of Drp-1-mediated mitochondrial fission and mitochondrial-derived ROS signaling. Cell Death Dis. 2014 Aug 14;5(8):e1368. doi: 10.1038/cddis.2014.320. PMID: 25118928; PMCID: PMC4454299.
2. Reith AD, Bamborough P, Jandu K, Andreotti D, Mensah L, Dossang P, Choi HG, Deng X, Zhang J, Alessi DR, Gray NS. GSK2578215A; a potent and highly selective 2-arylmethyloxy-5-substitutent-N-arylbenzamide LRRK2 kinase inhibitor. Bioorg Med Chem Lett. 2012 Sep 1;22(17):5625-9. doi: 10.1016/j.bmcl.2012.06.104. Epub 2012 Jul 7. PMID: 22863203; PMCID: PMC4208292.
In vitro protocol:
1. Saez-Atienzar S, Bonet-Ponce L, Blesa JR, Romero FJ, Murphy MP, Jordan J, Galindo MF. The LRRK2 inhibitor GSK2578215A induces protective autophagy in SH-SY5Y cells: involvement of Drp-1-mediated mitochondrial fission and mitochondrial-derived ROS signaling. Cell Death Dis. 2014 Aug 14;5(8):e1368. doi: 10.1038/cddis.2014.320. PMID: 25118928; PMCID: PMC4454299.
2. Reith AD, Bamborough P, Jandu K, Andreotti D, Mensah L, Dossang P, Choi HG, Deng X, Zhang J, Alessi DR, Gray NS. GSK2578215A; a potent and highly selective 2-arylmethyloxy-5-substitutent-N-arylbenzamide LRRK2 kinase inhibitor. Bioorg Med Chem Lett. 2012 Sep 1;22(17):5625-9. doi: 10.1016/j.bmcl.2012.06.104. Epub 2012 Jul 7. PMID: 22863203; PMCID: PMC4208292.
In vivo protocol:
1. Reith AD, Bamborough P, Jandu K, Andreotti D, Mensah L, Dossang P, Choi HG, Deng X, Zhang J, Alessi DR, Gray NS. GSK2578215A; a potent and highly selective 2-arylmethyloxy-5-substitutent-N-arylbenzamide LRRK2 kinase inhibitor. Bioorg Med Chem Lett. 2012 Sep 1;22(17):5625-9. doi: 10.1016/j.bmcl.2012.06.104. Epub 2012 Jul 7. PMID: 22863203; PMCID: PMC4208292.
1: Yan J, Almilaji A, Schmid E, Elvira B, Shimshek DR, van der Putten H, Wagner CA, Shumilina E, Lang F. Leucine-rich repeat kinase 2-sensitive Na+/Ca2+ exchanger activity in dendritic cells. FASEB J. 2015 May;29(5):1701-10. doi: 10.1096/fj.14-264028. Epub 2015 Jan 21. PubMed PMID: 25609428.
2: Saez-Atienzar S, Bonet-Ponce L, Blesa JR, Romero FJ, Murphy MP, Jordan J, Galindo MF. The LRRK2 inhibitor GSK2578215A induces protective autophagy in SH-SY5Y cells: involvement of Drp-1-mediated mitochondrial fission and mitochondrial-derived ROS signaling. Cell Death Dis. 2014 Aug 14;5:e1368. doi: 10.1038/cddis.2014.320. PubMed PMID: 25118928.
3: Reith AD, Bamborough P, Jandu K, Andreotti D, Mensah L, Dossang P, Choi HG, Deng X, Zhang J, Alessi DR, Gray NS. GSK2578215A; a potent and highly selective 2-arylmethyloxy-5-substitutent-N-arylbenzamide LRRK2 kinase inhibitor. Bioorg Med Chem Lett. 2012 Sep 1;22(17):5625-9. doi: 10.1016/j.bmcl.2012.06.104. Epub 2012 Jul 7. PubMed PMID: 22863203; PubMed Central PMCID: PMC4208292.
