| Description |
MIPS521 is a positive allosteric modulator of adenosine A1 receptor (A1AR). MIPS521 also has a lower A1R allosteric affinity (pKB=4.95). MIPS521 exhibits pain-relieving effects in vivo[1][2].
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| Related Catalog |
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| Target |
A1AR
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| In Vitro |
MIPS521 (compound 13o) (3-10 μM) improves the ability of R-PIA to promote A1AR-mediated ERK1/2 phosphorylation[1]. MIPS521 (0.3-30 μM; pretreament for 10 min, co-treatment for 30 min) produces a concentration-dependent potentiation of signalling by ADO in an inhibition of cAMP assay (expressed as a percentage of the inhibition of 3 μM forskolin-mediated cAMP) in CHO cells[2].
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| In Vivo |
MIPS521 (1-30 μg in 10 μL; intrathecal administration) reverses mechanical hyperalgesia in rats, promoting robust antinociception[2]. MIPS521 (10 μg in 10 μL; intrathecal administration) significantly reduces spontaneous pain in a conditioned place preference model[2]. MIPS521 (1-30 μg in 10 μL; intrathecal administration) reduces eEPSCs in spinal cord from nerve-injured rats, with a pEC50 of 6.9. The maximum MIPS521-induced decrease in synaptic current amplitude is significantly greater in nerve-injured rats than in sham surgery controls[2]. Animal Model: Male and female Sprague-Dawley rats (7-12 weeks) were performed a partial nerve ligation (PNL) or sham surgery[2] Dosage: 1, 3, 10, 30 μg in 10 μL Administration: Intrathecal administration Result: Reduced eEPSCs in spinal cord from nerve-injured rats and reversed mechanical hyperalgesia.
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| References |
[1]. Aurelio L, et, al. Allosteric modulators of the adenosine A1 receptor: synthesis and pharmacological evaluation of 4-substituted 2-amino-3-benzoylthiophenes. J Med Chem. 2009 Jul 23;52(14):4543-7. [2]. Draper-Joyce CJ, et, al. Positive allosteric mechanisms of adenosine A 1 receptor-mediated analgesia. Nature. 2021 Sep;597(7877):571-576.
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