L-755,507

L755507 is a potent, selective agonist of β3-AR with an IC50 of 35 nM.

Signaling Pathways >> GPCR/G Protein >> Adrenergic Receptor

Research Areas >> Cancer

IC50: 35 nM (β3-AR)[1]

L755507 causes a robust concentration-dependent increase in cAMP accumulation (pEC50 values of 8.5 and 12.3, respectively). Maximal cAMP accumulation with zinterol and L755507 is increased after pretreatment with pertussis toxin. In contrast to cAMP, zinterol, L755507 and L748337 increase phosphorylation of extracellular signal-regulated kinase 1/2 (Erk1/2) with very high potency (pEC50 values of 10.9, 11.7 and 11.6)[1]. L755507 and Scr7 do not reduce cell viability significantly. Scr7 does not affect cell cycle distribution in a range of 10 to 200 μM. L755507 significantly decreases the proportion of cells in the G2/M phase at 10 μM or 40 μM and increases the S-phase cells at 10 μM compare with the DMSO-treated cells[2].

The cytosensor microphysiometer is used to measure β3-AR-mediated increases in ECAR . In brief, CHO β3 cells are seeded into 12-mm Transwell inserts at 5×105 cells/cup and left to adhere overnight. On the day of experiment, cells are equilibrated for 2 h, and cumulative concentration-response curves to L755507, zinterol, or L748337 are constructed in paired sister cells with each concentration of drug exposed to cells for 14 min. Results are expressed as a percentage of the maximal response to L755507. In experiments examining the effect of inhibitors, cells are treated for 30 min before stimulation with appropriate drugs. All drugs are diluted in modified RPMI 1640 medium. These results are expressed as a percentage of the maximal response to L755507, zinterol, or L748337 over basal[1].

[1]. Sato M, et al. The beta3-adrenoceptor agonist 4-[[(Hexylamino)carbonyl]amino]-N-[4-[2-[[(2S)-2-hydroxy-3-(4-hydroxyphenoxy)propyl]amino]ethyl]-phenyl]-benzenesulfonamide (L755507) and antagonist (S)-N-[4-[2-[[3-[3-(acetamidomethyl)phenoxy]-2-hydroxypropyl]amino]-ethyl]phenyl]benzenesulfonamide (L748337) activate different signaling pathways in Chinese hamster ovary-K1 cells stably expressing the human beta3-adrenoceptor. Mol Pharmacol. 2008 Nov;74(5):1417-28.

[2]. Guoling Li, et al. Small molecules enhance CRISPR/Cas9-mediated homology-directed genome editing in primary cells. Sci Rep. 2017; 7: 8943.

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