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Chemical Structure| 160098-96-4 Chemical Structure| 160098-96-4

Structure of SCH58261
CAS No.: 160098-96-4

Chemical Structure| 160098-96-4

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SCH 58261 is a potent and selective A2a adenosine receptor antagonist with Ki of 2.3 nM and 2 nM for rat A2a and bovine A2a, respectively.

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Product Details of SCH58261

CAS No. :160098-96-4
Formula : C18H15N7O
M.W : 345.36
SMILES Code : NC1=NC(N(CCC2=CC=CC=C2)N=C3)=C3C4=NC(C5=CC=CO5)=NN14
MDL No. :MFCD00933778
InChI Key :UTLPKQYUXOEJIL-UHFFFAOYSA-N
Pubchem ID :176408

Safety of SCH58261

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of SCH58261

GPCR

Isoform Comparison

Biological Activity

Target
  • Adenosine Receptor

    rat A2a, Ki:2.3 nM

    bovine A2a, Ki:2.0 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
Hippocampal slices 10 nM 20 minutes SCH58261 prevented the CX3CL1-induced potentiation of NMDA-fEPSPs, indicating that A2AR activity is crucial for CX3CL1-mediated modulation of NMDARs. PMC3765929
N9 microglial cells 50 nM 6 hours SCH58261 prevented the LPS-induced decrease of mBDNF, indicating that A 2AR plays a key role in LPS-induced BDNF secretion. PMC3567964
Xenopus oocytes 10 nM SCH58261 reduced IGABA run-down in ∼40% of tested oocytes but increased it in ∼20% of tested oocytes. PMC2567502

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice Spinal cord injury model Intraperitoneal injection 0.3 mg/kg DAC and 10 mg/kg TAK-243 three times per week until recipient mice died SCH58261 protects against spinal cord injury by acting on centrally located A2A receptors, likely reducing excitotoxicity. PMC3096915
Mice Head and neck squamous cell carcinoma (HNSCC) mouse model Intraperitoneal injection 50 mg/kg/day Once daily for 16 days SCH58261 significantly delayed tumor growth in the HNSCC mouse model and significantly reduced the population of CD4+Foxp3+ regulatory T cells, enhancing the anti-tumor response of CD8+ T cells PMC5461710
BALB/c nu/nu mice OSCC xenograft model Intraperitoneal injection 1 mg/kg Every other day for 25 days SCH58261 impeded the growth of OSCC xenograft by blocking trigeminal A2AR signaling and reduced the release of CGRP. PMC11183250
C57BL/6 mice IE9mp1-mIDO1 ovarian cancer model Intraperitoneal injection 50 mg/kg·d From GD9 to GD18, once daily To test whether the combination of IDO1 inhibitor and A2a/A2b receptor antagonists could improve the survival rate of ovarian cancer-bearing mice. The results showed that the combination of IDO1 inhibitor and A2a/A2b receptor antagonists significantly improved the survival rate of mice. PMC9311231
Mice Chronic unpredictable stress (CUS) model Intraperitoneal injection 5 mg/kg Daily until the end of the experiment SCH58261 treatment reversed the CUS-induced behavioral and synaptic dysfunction, restoring performance in the forced swimming test, elevated plus maze test, and modified Y maze test, and restored the density of synaptic markers and the amplitude of long-term potentiation (LTP) in the hippocampus. PMC4485143
Mice Experimental autoimmune encephalomyelitis (EAE) model Intraperitoneal and subcutaneous injection 1mg/kg 5 days on, 2 days off, from day 7 to day 21 To evaluate the protective effect of SCH58261 on EAE progression, results showed that SCH58261 significantly protected mice from EAE development PMC2453691
C57BL/6 and BALB/c mice Orthotopic liver tumor model Intraperitoneal injection 0.1 mg/kg Once daily for 3 weeks Combination of SCH58261 with anti-PD1 therapy showed stronger anti-tumor effects in orthotopic liver tumor models, while SCH58261 monotherapy was ineffective. PMC10772255

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.90mL

0.58mL

0.29mL

14.48mL

2.90mL

1.45mL

28.96mL

5.79mL

2.90mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

[1]Paterniti I, Melani A, et al. Selective adenosine A2A receptor agonists and antagonists protect against spinal cord injury through peripheral and central effects. J Neuroinflammation. 2011 Apr 12;8:31.

[2]Zocchi C, Ongini E, et al. The non-xanthine heterocyclic compound SCH 58261 is a new potent and selective A2a adenosine receptor antagonist. J Pharmacol Exp Ther. 1996 Feb;276(2):398-404.

[3]Pagnussat N, Almeida AS, et al. Adenosine A(2A) receptors are necessary and sufficient to trigger memory impairment in adult mice. Br J Pharmacol. 2015 Aug;172(15):3831-45.

[4]Hsu CW, Wang CS, et al. Caffeine and a selective adenosine A2A receptor antagonist induce sensitization and cross-sensitization behavior associated with increased striatal dopamine in mice. J Biomed Sci. 2010 Jan 15;17:4.

[5]El Yacoubi M, Ledent C, et al. SCH 58261 and ZM 241385 differentially prevent the motor effects of CGS 21680 in mice: evidence for a functional 'atypical' adenosine A(2A) receptor. Eur J Pharmacol. 2000 Jul 28;401(1):63-77.

[6]Popoli P, Pintor A, et al. Blockade of striatal adenosine A2A receptor reduces, through a presynaptic mechanism, quinolinic acid-induced excitotoxicity: possible relevance to neuroprotective interventions in neurodegenerative diseases of the striatum. J Neurosci. 2002 Mar 1;22(5):1967-75.

[7]Wardas J, Pietraszek M, et al. SCH 58261, a selective adenosine A2A receptor antagonist, decreases the haloperidol-enhanced proenkephalin mRNA expression in the rat striatum. Brain Res. 2003 Jul 11;977(2):270-7.

[8]Leite MR, Wilhelm EA, et al. Protective effect of caffeine and a selective A2A receptor antagonist on impairment of memory and oxidative stress of aged rats. Exp Gerontol. 2011 Apr;46(4):309-15.

[9]Yang M, Soohoo D, et al. Characterization of the potency, selectivity, and pharmacokinetic profile for six adenosine A2A receptor antagonists. Naunyn Schmiedebergs Arch Pharmacol. 2007 Apr;375(2):133-44. Epub 2007 Feb 20.

[10]Varani K. Pharmacological and biochemical characterization of purified A2a adenosine receptors in human platelet membranes by [3H]-CGS 21680 binding. Br J Pharmacol. 1996 Apr;117(8):1693-701.

[11]Zocchi C. The non-xanthine heterocyclic compound SCH 58261 is a new potent and selective A2a adenosine receptor antagonist. J Pharmacol Exp Ther. 1996 Feb;276(2):398-404.

[12]Kuzumaki N. Multiple analyses of G-protein coupled receptor (GPCR) expression in the development of gefitinib-resistance in transforming non-small-cell lung cancer. PLoS One. 2012;7(10):e44368. doi: 10.1371/journal.pone.0044368.

[13] Zocchi C. The non-xanthine heterocyclic compound SCH 58261 is a new potent and selective A2a adenosine receptor antagonist. J Pharmacol Exp Ther. 1996 Feb;276(2):398-404.

[14]Paterniti I. Selective adenosine A2A receptor agonists and antagonists protect against spinal cord injury through peripheral and central effects. J Neuroinflammation. 2011 Apr 12;8:31. doi: 10.1186/1742-2094-8-31.

[15]Reyhani-Rad S, Mahmoudi J. Effect of adenosine A2A receptor antagonists on motor disorders induced by 6-hydroxydopamine in rat. Acta Cir Bras. 2016 Feb;31(2):133-7.

 

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