6-[(1-NaphthalenylMethyl)thio]-9H-purine

Description

PU 02 is an antagonist of the serotonin (5-HT) receptor subtype 5-HT₃ with IC₅₀ values ranging from 0.36 to 1.3 μM for human 5-HT_3A, 5-HT_3AB, 5-HT_3AC, and 5-HT_3AE in a FLIPR membrane potential assay using HEK293 cells expressing human recombinant receptors. It is selective for 5-HT₃ over other Cys-loop containing receptors with IC₅₀ values >100 μM for mouse, rat, and human nicotinic (nACh), human GABA_A, and human glycine (Gly) receptors. PU 02 inhibits currents induced by 5-HT in COS-7 cells expressing human 5-HT_3A (IC₅₀ = 0.49 μM). PU 02 also reduces growth of HepG2 cells in a dose-dependent manner via induction of cell cycle arrest at the G₂/M phase and apoptosis.

Uses

PU02, a derivative of 6-MP (HY-13677), is a negative allosteric modulator (NAM) of 5-HT3 receptor, with IC50 values of 0.36 and 0.73 μM in HEK293 cells transfected with human 5-HT3A and 5-HT3AB receptors respectively[1][2].

IC 50

5-HT_3A Receptor: 0.36 μM (IC₅₀); 5-HT ₃ AB: 0.73 μM (IC₅₀)

References

[1] Sarah M Trattnig, et al. Discovery of a novel allosteric modulator of 5-HT3 receptors: inhibition and potentiation of Cys-loop receptor signaling through a conserved transmembrane intersubunit site. J Biol Chem. 2012 Jul 20;287(30):25241-54. DOI:10.1074/jbc.M112.360370
[2] Xiao-Guang Yang, et al. 6-[(1-naphthylmethyl)sulfanyl]-9H-purine induces G2/M phase arrest and apoptosis in human hepatocellular carcinoma HepG2 cells. Eur J Pharmacol. 2012 Nov 15;695(1-3):27-33. DOI:10.1016/j.ejphar.2012.09.004