GSK2578215A | CAS#1285515-21-0 | LRRK2 inhibitor

GSK2578215A
featured

WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 406662

CAS#: 1285515-21-0

Description: GSK2578215A is a potent and highly selective LRRK2 kinase inhibitor. GSK2578215A induces protective autophagy in SH-SY5Y cells: involvement of Drp-1-mediated mitochondrial fission and mitochondrial-derived ROS signaling.Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been associated with Parkinson's disease, and its inhibition opens potential new therapeutic options. GSK2578215A induces mitochondrial fragmentation of an early step preceding autophagy. GSK2578215A induced oxidative stress as evidenced by the accumulation of 4-hydroxy-2-nonenal in SH-SY5Y cells.

Chemical Structure

GSK2578215A

CAS# 1285515-21-0

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 406662
Name: GSK2578215A
CAS#: 1285515-21-0
Chemical Formula: C24H18FN3O2
Exact Mass: 399.14
Molecular Weight: 399.425
Elemental Analysis: C, 72.17; H, 4.54; F, 4.76; N, 10.52; O, 8.01

Price and Availability

Size	Price	Availability
25mg	USD 250	2 Weeks
50mg	USD 450	2 Weeks
100mg	USD 750	2 Weeks
200mg	USD 1250	2 Weeks
500mg	USD 2650	2 Weeks
1g	USD 3750	2 Weeks
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: GSK2578215A; GSK-2578215A; GSK 2578215A.

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

Appearance: Solid powder

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

More Info:

Product Data:

Product Data

Instruction:

View handling instruction

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/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. 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

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.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.

Mass

Concentration

Volume

M. Wt* g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

Volume (to add to vial)

Mass (in vial)

Desired Reconstitution Concentration

Dilution Calculator

Calculate the dilution required to prepare a stock solution.

Concentration 1

Volume 1

Concentration 2

Volume 2

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.

Your view history

GSK2578215A featured