Synonym
A-804598; A 804598; A804598.
IUPAC/Chemical Name
N-Cyano-N′′-[(1S)-1-phenylethyl]-N′-5-quinolinyl-guanidine
InChi Key
PQYCRDPLPKGSME-AWEZNQCLSA-N
InChi Code
InChI=1S/C19H17N5/c1-14(15-7-3-2-4-8-15)23-19(22-13-20)24-18-11-5-10-17-16(18)9-6-12-21-17/h2-12,14H,1H3,(H2,22,23,24)/t14-/m0/s1
SMILES Code
C[C@H](/N=C(NC1=C2C=CC=NC2=CC=C1)/NC#N)C3=CC=CC=C3
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
>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:
A-804598 is a CNS penetrant, competitive and selective P2X7 receptor antagonist with IC50s of 9 nM, 10 nM and 11 nM for mouse, rat and human P2X7 receptors, respectively.
In vitro activity:
To determine the involvement of P2X7R in activation of JAK1/STAT3 signaling, this study exposed FLSs to 10 ng/mL TNF-α in the presence or absence of 10 and 20 µM A804598 for 2 h. Using β-actin as a control, the results of western blot analysis in Figure 8 show that TNF-α induced significant phosphorylation of both JAK1 and STAT3 protein by approximately 5-fold basal levels, while total JAK1 and STAT3 remained constant. However, treatment with A804598 could ameliorate TNF-α-induced phosphorylation of JAK1/STAT3 in a dose-dependent manner, with the higher dose reducing p-JAK1/STAT3 to roughly 2-fold basal levels. These findings suggest a novel role of A804598 in ameliorating inflammation via modulation of the JAK1/STAT3 signaling pathway.
Reference: Am J Transl Res. 2020; 12(1): 45–53. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013224/
In vivo activity:
H&E staining showed significant liver steatosis after Hybrid exposure (Fig. 7a). There was a large increase in fat deposits calculated as the ratio of white areas versus background color with the adjusted threshold. A804598 treatment did not affect the extent of the steatosis (Fig. 7a). Hybrid exposure caused increases in pro-inflammatory markers in liver. There were significant increases in mRNA for Tnfα, Ccl2 and Nos2. These increases were abolished by administration of A804598 (Fig. 7b).
Reference: J Neuroimmune Pharmacol. 2019 Jun; 14(2): 263–277. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494709/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
39.1 |
124.10 |
| DMSO:PBS (pH 7.2) (1:20) |
0.1 |
0.16 |
| DMF |
30.0 |
95.12 |
| Ethanol |
6.0 |
19.02 |
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
315.38
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. Liu Y, Wu Y, Gu S, Yin Q, Li H, Wang J, Geng D, Xu Y. The P2X7 receptor (P2X7R)-specific antagonist A804598 inhibits inflammatory reaction in human fibroblast-like synoviocytes. Am J Transl Res. 2020 Jan 15;12(1):45-53. PMID: 32051736; PMCID: PMC7013224.
2. Donnelly-Roberts DL, Namovic MT, Surber B, Vaidyanathan SX, Perez-Medrano A, Wang Y, Carroll WA, Jarvis MF. [3H]A-804598 ([3H]2-cyano-1-[(1S)-1-phenylethyl]-3-quinolin-5-ylguanidine) is a novel, potent, and selective antagonist radioligand for P2X7 receptors. Neuropharmacology. 2009 Jan;56(1):223-9. doi: 10.1016/j.neuropharm.2008.06.012. Epub 2008 Jun 17. PMID: 18602931.
3. Freire D, Reyes RE, Baghram A, Davies DL, Asatryan L. P2X7 Receptor Antagonist A804598 Inhibits Inflammation in Brain and Liver in C57BL/6J Mice Exposed to Chronic Ethanol and High Fat Diet. J Neuroimmune Pharmacol. 2019 Jun;14(2):263-277. doi: 10.1007/s11481-018-9816-3. Epub 2018 Oct 23. PMID: 30353422; PMCID: PMC6494709.
4. Catanzaro JM, Hueston CM, Deak MM, Deak T. The impact of the P2X7 receptor antagonist A-804598 on neuroimmune and behavioral consequences of stress. Behav Pharmacol. 2014 Sep;25(5-6):582-98. doi: 10.1097/FBP.0000000000000072. PMID: 25083574.
In vitro protocol:
1. Liu Y, Wu Y, Gu S, Yin Q, Li H, Wang J, Geng D, Xu Y. The P2X7 receptor (P2X7R)-specific antagonist A804598 inhibits inflammatory reaction in human fibroblast-like synoviocytes. Am J Transl Res. 2020 Jan 15;12(1):45-53. PMID: 32051736; PMCID: PMC7013224.
2. Donnelly-Roberts DL, Namovic MT, Surber B, Vaidyanathan SX, Perez-Medrano A, Wang Y, Carroll WA, Jarvis MF. [3H]A-804598 ([3H]2-cyano-1-[(1S)-1-phenylethyl]-3-quinolin-5-ylguanidine) is a novel, potent, and selective antagonist radioligand for P2X7 receptors. Neuropharmacology. 2009 Jan;56(1):223-9. doi: 10.1016/j.neuropharm.2008.06.012. Epub 2008 Jun 17. PMID: 18602931.
In vivo protocol:
1. Freire D, Reyes RE, Baghram A, Davies DL, Asatryan L. P2X7 Receptor Antagonist A804598 Inhibits Inflammation in Brain and Liver in C57BL/6J Mice Exposed to Chronic Ethanol and High Fat Diet. J Neuroimmune Pharmacol. 2019 Jun;14(2):263-277. doi: 10.1007/s11481-018-9816-3. Epub 2018 Oct 23. PMID: 30353422; PMCID: PMC6494709.
2. Catanzaro JM, Hueston CM, Deak MM, Deak T. The impact of the P2X7 receptor antagonist A-804598 on neuroimmune and behavioral consequences of stress. Behav Pharmacol. 2014 Sep;25(5-6):582-98. doi: 10.1097/FBP.0000000000000072. PMID: 25083574.
1: Lord B, Ameriks MK, Wang Q, Fourgeaud L, Vliegen M, Verluyten W, Haspeslagh P,
Carruthers NI, Lovenberg TW, Bonaventure P, Letavic MA, Bhattacharya A. A novel
radioligand for the ATP-gated ion channel P2X7: [3H] JNJ-54232334. Eur J
Pharmacol. 2015 Oct 15;765:551-9. doi: 10.1016/j.ejphar.2015.09.026. PubMed PMID:
26386289.
2: Antonioli L, Giron MC, Colucci R, Pellegrini C, Sacco D, Caputi V, Orso G,
Tuccori M, Scarpignato C, Blandizzi C, Fornai M. Involvement of the P2X7
purinergic receptor in colonic motor dysfunction associated with bowel
inflammation in rats. PLoS One. 2014 Dec 30;9(12):e116253. doi:
10.1371/journal.pone.0116253. PubMed PMID: 25549098; PubMed Central PMCID:
PMC4280204.
3: Catanzaro JM, Hueston CM, Deak MM, Deak T. The impact of the P2X7 receptor
antagonist A-804598 on neuroimmune and behavioral consequences of stress. Behav
Pharmacol. 2014 Sep;25(5-6):582-98. doi: 10.1097/FBP.0000000000000072. PubMed
PMID: 25083574.
4: Able SL, Fish RL, Bye H, Booth L, Logan YR, Nathaniel C, Hayter P, Katugampola
SD. Receptor localization, native tissue binding and ex vivo occupancy for
centrally penetrant P2X7 antagonists in the rat. Br J Pharmacol. 2011
Jan;162(2):405-14. doi: 10.1111/j.1476-5381.2010.01025.x. PubMed PMID: 20840537;
PubMed Central PMCID: PMC3031061.
5: Donnelly-Roberts DL, Namovic MT, Surber B, Vaidyanathan SX, Perez-Medrano A,
Wang Y, Carroll WA, Jarvis MF. [3H]A-804598
([3H]2-cyano-1-[(1S)-1-phenylethyl]-3-quinolin-5-ylguanidine) is a novel, potent,
and selective antagonist radioligand for P2X7 receptors. Neuropharmacology. 2009
Jan;56(1):223-9. doi: 10.1016/j.neuropharm.2008.06.012. PubMed PMID: 18602931.
