A-804598
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MedKoo CAT#: 530351

CAS#: 1125758-85-1

Description: A-804598 represents a structurally novel, competitive, and selective antagonist that has equivalent high affinity at rat (IC50 = 10 nM), mouse (IC50 = 9 nM) and human (IC50 = 11 nM) P2X7 receptors and also potently blocked agonist stimulated release of IL-1beta and Yo-Pro uptake from differentiated THP-1 cells that natively express human P2X7 receptors. A-804598 is one of the most potent and selective antagonists for mammalian P2X7 receptors described to date and [3H]A-804598 is a high affinity antagonist radioligand that specifically labels rat P2X7 receptors.


Chemical Structure

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A-804598
CAS# 1125758-85-1

Theoretical Analysis

MedKoo Cat#: 530351
Name: A-804598
CAS#: 1125758-85-1
Chemical Formula: C19H17N5
Exact Mass: 315.15
Molecular Weight: 315.380
Elemental Analysis: C, 72.36; H, 5.43; N, 22.21

Price and Availability

Size Price Availability Quantity
25mg USD 150
50mg USD 250
100mg USD 450
200mg USD 850
500mg USD 1650
1g USD 2850
2g USD 4650
5g USD 6650
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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

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

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:
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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. 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

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.

Recalculate based on batch purity %
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.

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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.