CLH304a (compound 14) is a specific and noncompetitive GABA B receptor negative allosteric modulator (NAM). CLH304a decreases GABA-induced IP3 production with an IC50 of 37.9 μM. CLH304a has no effect on other GPCR Class C members such as mGluR1, mGluR2, and mGluR5. CLH304a acts on the heptahelical domain of GB2 subunits and non-competitively inhibits the effect of agonists with inverse agonist properties. CLH304a inhibits Baclofen -induced ERK1/2 phosphorylation in HEK293 cells overexpressing GABA B receptor [1] [2].
In Vitro, (E)-GABAB receptor antagonist 1 (compound 14) decreases agonist GABA-induced maximal effect of IP3 production in HEK293 cells overexpressing GABAB receptors and Gqi9 proteins without changing the EC50[1].
References:
[1]. Chen LH, et al. Discovery of a Negative Allosteric Modulator of GABAB Receptors. ACS Med Chem Lett. 2014 May 27;5(7):742-7.
[2]. Bing Sun, et al. A negative allosteric modulator modulates GABAB-receptor signalling through GB2 subunits. Biochem J. 2016 Mar 15;473(6):779-87.
In Vitro, (E)-GABAB receptor antagonist 1 (compound 14) decreases agonist GABA-induced maximal effect of IP3 production in HEK293 cells overexpressing GABAB receptors and Gqi9 proteins without changing the EC50[1].
References:
[1]. Chen LH, et al. Discovery of a Negative Allosteric Modulator of GABAB Receptors. ACS Med Chem Lett. 2014 May 27;5(7):742-7.
[2]. Bing Sun, et al. A negative allosteric modulator modulates GABAB-receptor signalling through GB2 subunits. Biochem J. 2016 Mar 15;473(6):779-87.